TY  - JOUR
A1  - Karppanen, H.
A1  - Sirén, Anna-Leena
A1  - Eskeli-Kaivosoja, Alice
T1  - Central cardiovascular and thermal effects of Prostaglandin F2α in rats
N2  - Administration of PGF 2IX (0.2-6.4 J.lg) into the lateral cerebral ventricle (i.c.v.) induced dosedependent increases in blood pressure , heart rate and body temperature in urethane-anaesthetised rats, but had no effect on these parameters when the same dose range was administered intravenously. Peripheral pretreatment with sodium meclofenamate (50 mg/kg s.c.) sltifted all the dose-response curves for PGF 2IX (i.c.v.) to the left, but indomethacin (50 mg/kg s.c.) did not significantly affect those changes. Central pretreatment with sodiurn meclofenamate or indomethacin (1.25 mg per rat i.c.v.) failed to modify significantly the effects of centrally administered PGF 2IX' The results support previous suggestions that PGF 2IX may participate in the central control of the cardiovascular and thermoregulatory systems, and also suggest that there may be differences in the sites and/or modes of action between sodiurn meclofenamate and indomethacin.
KW  - Prostaglandine
Y1  - 1979
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-47955
ER  - 
TY  - JOUR
A1  - Sirén, Anna-Leena
A1  - Karppanen, H.
T1  - Influence of analgesic antipyretics on the central cardiovascular effects of clonidine in rats
N2  - No abstract available
KW  - Prostaglandine
Y1  - 1980
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-48640
ER  - 
TY  - JOUR
A1  - Sirén, Anna-Leena
T1  - Central cardiovascular and thermal effects of prostacyclin in rats
N2  - Prostacyclin (PGI2) induced a dose-dependent decrease in blood pressure with slight increases in heart rate and body temperature, when administered at the doses of 0.1-100 ~g into the lateral cerebral ventricle (i.c.v.) of the urethane-anaesthetised rat. When the same doses were administered intravenously, both the blood pressure and heart rate decreased. Central pretreatment wib~ sodiurn meclofenamate (1 mg/rat i.c.v.) antagonised the central hypotensive effect of PGI2 but i.c.v. pretreatrnent of the rats with indomethacin (1 mg/rat) failed to affect the PGI 2-induced hypotension. Central pretreatment with two histamine H2-receptor antagonists, cimetidine (500 ~g/rat i.c.v.) or metiamide (488 ~g/rat i.c.v.), antagonised the blood pressure lowering effect of 0.1 ~g dose of PGI2 but failed to affect the hypotension induced by higher PGI2 doses. Therefore the main central hypotensive effect of PGI2 seems not to be associated with the stimulation of histamine H2 -receptors in the brain. The hypotensive effect of i.c.v. administered PGI2 appears to be due to an action upon the central nervous system rather than to a leakage into the peripheral circulation. This assurnption is supported by the fact that sodiurn meclofenamate i.c.v. antagonised the effect of PGI 2. In addition, the chronotropic response to i.c.v. PGI2 was opposite to that induced by intravenous administration. The results also suggest that there may be differences in the mode of action between sodiurn meclofenamate and indomethacin.
KW  - Prostaglandine
Y1  - 1981
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-47943
ER  - 
TY  - JOUR
A1  - Sirén, Anna-Leena
T1  - Differences in central actions of arachidonic acid and prostaglandin F\(_{2\alpha}\) between spontaneously hypertensive and normotensive rats
N2  - Prostag1andin F\(_{2\alpha}\) (PGF\(_{2\alpha}\)) is one of the most common metabo1ites of arachidonic acid (M) in rat brain. When administered intracerebroventricularly (i.c.v.) to rats, both AA and PGFal exert dose-related hypertensive, tachycardic and hyperthermic effects. Metabolie alterations in the endogenaus formation of some prostaglandins in the brain-stem of spontaneously hypertensive rats (SHR) have been reported. Therefore the central effects of AA and PGF \(_{2\alpha}\) on blood pressure, heart rate and body temperature were studied both in SHR and nonootensive Wistar rats (NR) under urethane-anaesthesia. The hypertensive effect of AA i.c.v. (0.01-100 \(\mu\)g/rat) was larger in magni tude in SHR than in NR, but there was no significant difference in the M-induced changes of heart rate and body temperature between the groups. Pretreatment of NR wi th soditm1 :meclofenamate (1 mg/rat i.c.v.) antagonised the central effects of M indicating that these effects are not due to M itself but to its conversion to prostaglandins. Unlike the effects of AA, the central hypertensive, tachycardic and hyperthennic responses to PGF\(_{2\alpha}\) (0.5-50 l-lg/rat i.c.v .) were significantly attenuated in SHR. The present results obtained with M are conpatible with the previous assumption that the synthesis of prostaglandins in the brain of SHR might differ from that in NR. The results also demonstrate that the central effects of PGF\(_{2\alpha}\) are reduced in SHR.
KW  - Neurobiologie
Y1  - 1982
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-63324
ER  - 
TY  - JOUR
A1  - Sirén, Anna-Leena
T1  - Central cardiovascular and thermal effects of Prostaglandin E2 in rats
N2  - Prostaglandin E2 (PGE2) increased the blood pressure, heart rate and body temperature, when administered at the doses ofO.OOI-IO,ug into the lateral cerebral ventricle (i.c.v.) of the urethane-anesthetised rat. The highest dose of 10 ,ug/rat induced a strong initial hypotensive effect. lntravenously (i.v.), PGE2 at the doses of 0.01-10 ,ug/rat caused a biphasic blood pressure response with dose-related initial decreases followed by slight increases in blood pressure. The heart rate and body temperature were slightly increased by i.v. administrations of PGE2 . The highest i.v. dose of 10 ,ug/rat initially decreased also the heart rate. Central pretreatment with indomethacin ( I mg/rat i.c.v.) partly antagonised all of the recorded central effects of PGE2 , while sodium meclofenamate (I mg/rat i.c. v.) abolished the hypertensive response to i.c. v. administered PGE2 but failed to significantly affect the PGE2-induced rises of heart rate and body temperature. The results support the previous suggestions that PGE2 may participate in the central cardiovascular and thermoregulatory contro!. The results also suggest that indomethacin and sodium meclofenamate antagonize the effects of exogenous prostaglandins. Since sodium meclofenamate, unlike indomethacin, affected preferentially the hypertensive response to centrally administered PGE2 , there may be differences in the sites and/or modes of action between these drugs.
KW  - Physiologie
Y1  - 1982
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-47960
ER  - 
TY  - JOUR
A1  - Sirén, Anna-Leena
T1  - Central cardiovascular and thermal effects of prostaglandin D2 in rats
N2  - Prostaglandin D2 (PGD2) is the most common prostaglandin type of tile rat brain. Recently a neurornodulator role for PGD2 has been suggested. In the present work the central cardiovascular and thermal effects of PGDz were studied in urethane-anaesthetised rats. Mlen adrndnistered at the doses of 0.001-10 ~g/rat into the lateral cerebral ventricle(i.c.v.), PGD2 slightly increased the blood pressure, heart rate and body ternpera~ ure. The highest dose caused also an initial hypotensive effect. Upon lntravenous injections PGD2 (0.1-10 ~g/rat) initially decreased and then weakly increased the blood pressure but had only negligible effects on heart rate and body temperature. Central pretreatment with sodium meclofenamate or indomethacin (1 mg/rat i.c.v.) antagonised effectively all the recorded central effects of PGD2. The central cardiovascular and thermal effects of PGD2 were much weaker than those obtained earlier with other prostaglandins, such as PGF2alpha and PGE2.. Therefore, in spite of its abundance in the brain PGD2 may not be very important for the central cardiovascular and thermal regulation in the rat.
KW  - Medizin
Y1  - 1982
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-48658
ER  - 
TY  - JOUR
A1  - Sirén, Anna-Leena
A1  - Paakkari, I.
T1  - Cardiovascular effects of TRH i.c.v. in conscious rats
N2  - In addition to the endocrine effects, the thyrotropin releasing hormone (TRH) is known to induce dose-dependent increases in blood pressure and heart rate after intracerebroventricular (i.c.v.) administration in urethane-anaesthetised rats (1, 2). The a~ of the present study was to investigate whether TRH has similar effects in conscious rats of various strains i.e. spontaneously hypertensive rats (SHR), normotensive Wistar-Kyoto (WKY) and Wistar (NR) rats.
KW  - Medizin
Y1  - 1984
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-49071
ER  - 
TY  - JOUR
A1  - Sirén, Anna-Leena
A1  - Svarström-Fraser, M.
A1  - Paakkari, I.
T1  - Central cardiovascular effects of the endoperoxide analogue U-46619 i.c.v. in rats
N2  - Thromboxanes are abundantly present in the rat brain but their possible physiological functions in the brain are not known. The prostaglandin endoperoxide analogue U-46619 is a selective agonist of TxA2 receptors in many peripheral tissues. In the present study the ·central cardiovascular and ventilatory effects of U-46619 were investigated in rats. In conscious spontaneously hypertensive rats (SHR) U-46619 (1-100 nmol/kg i.c.v.) induced a strong dose-related increase in blood pressure but had no significant effect on heart rate. In conscious normotensive rats (NR) neither blood pressure nor heart rate was significantly affected. Furthermore, U-46619 (0.1-100 nmol/kg i.c.v.) had no significant effect on blood pressure, heart rate or ventilation in urethane-anaesthetised NR . The results demonstrate an increased sensitivity of SHR to TxA2.
KW  - Medizin
Y1  - 1985
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-49064
ER  - 
TY  - JOUR
A1  - Eimerl, J.
A1  - Sirén, Anna-Leena
A1  - Feuerstein, G.
T1  - Systemic and regional hemodynamic effects of leukotrienes D\(_4\) and E\(_4\) in the conscious rat
N2  - No abstract available
KW  - Neurobiologie
Y1  - 1986
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-63317
ER  - 
TY  - JOUR
A1  - Paakkari, I.
A1  - Nurminen, M-L.
A1  - Sirén, Anna-Leena
T1  - Cardioventilatory effects of TRH in anesthetized rats: role of the brainstem
N2  - Cardioventilator responses were studied in anaesthetized rats after injections of TRH into either the lateral (i.c.v. lat) or the fourth (i.c.v. IV) cerebral ventricles. TRH induced a morerapid hypertensive effect i.c.v. IV than i.c.v. lat. Blocking of the cerebral aqueduct abolished the hypertensive and tachypnoeic effects of TRH i.c.v. lat but not those of TRH i.c.v. IV. It is concluded that TRH increased blood pressure and ventilation rate via brain stem structures close to the fourtli ventricle.
KW  - Neurobiologie
KW  - TRH
KW  - Cardiovascular
KW  - Ventilation
KW  - Brain stem
Y1  - 1986
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-63277
ER  - 
TY  - JOUR
A1  - Sirén, Anna-Leena
A1  - Powell, E.
A1  - Feuerstein, G.
T1  - Thyrotropin releasing hormone in hypovolemia: a hemodynamic evaluation in the rat
N2  - ln the present study the effects of thyrotropin releasing hormone (TRH) and its stable analogue, CG3703, on cardiac output (thermodilution, Cardiomax) and regional blood flow (BF; directional pulsed Doppler technique) were investigated in hypovolemic hypotension in the rat. In urethan-anesthetized rats TRH (0.5 or 2 mg/ kg ia) or CG3703 (0.05 or 0.5 mg/kg ia) reversed the bleeding (27% of the blood volume)-induced decreases in mean arterial ...
KW  - Neurobiologie
KW  - cardiac output
KW  - total peripheral resistance
KW  - regional blood flow
Y1  - 1986
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-63288
ER  - 
TY  - JOUR
A1  - Sirén, Anna-Leena
A1  - Feuerstein, G.
T1  - Effect of T-2 toxin on regional blood flow and vascular resistance in the conscious rat
N2  - The acute effect ofT-2 toxemia on local blood flow and vascular resistance in hindquarter. mesenteric. and renal vascular beds was continuously measured by the directional pulsed Doppler technique in conscious, male Sprague-Dawley rats. Intravenous injection ofT-2 toxin (I mg/kg) in the conscious rat reduced blood flow and increased vascular resistance in all blood vessels studied but had no significant effect on mean arterial pressure or heart rate. The blood flow in hindquarters gradually decreased to a minimum of -77 ± 9% (mean ±SE) 6 hr after the toxin injection. The hindquarter vascular resistance concomitantly increased to a maximum value of + 323 ± 69% above thc resistance before toxin administration. Mesenteric and renal blood flow initially increased (slightly) and then gradually decreased. The maximum drop of blood flow, -90 ± 13% and -76 ± 13% for the mesenteric and renal vascular beds, respectively, was achieved 4 hr after T-2 toxin injection and the blood flow values remained low for up to 6 hr. Simultaneously with the impairment of
KW  - Neurobiologie
Y1  - 1986
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-63293
ER  - 
TY  - JOUR
A1  - Sirén, Anna-Leena
A1  - Feuerstein, G.
A1  - Labroo, V. M.
A1  - Coleen, L. A.
A1  - Lozovsky, D.
T1  - Effect of thyrotropin releasing hormone and some of its histidine analogs on the cardiovascular system and prolactin release in the conscious rat
N2  - The cardiovascular and endocrine activity of three analogs of thyrotropin releasing hor.mone (TRH), 4-nitro-imidazole TRH (4-nitroTRH), 2-trifluoro-methyl-imidazole TRH (2-TFM-TRH) and 4-trifluoromethyl- imidazole TRH (4-TFM-TRH), was compared to TRH in conscious rats. Injection of TRH or the three analogs (1 mg/kg or 5 mg/kg) into the arterial line induced increases in mean arterial pressure, pulse pressure and heart rate and raised plasma prolactin (PRL). None of the analogs were more potent than TRH in inducing cardiovascular changes. The 4-TFM-TRH was significantly less potent than the 2-TFM-TRH in increasing blood pressure, while the nitro-TRH was more potent than the 2-TFM-TRH in producing tachycardia. TRH induced a two-fold increase in PRL at the 5 mg/kg dose, while both the fluorinated analogs elici ted a 4 to 5 fold increase in PRL at the higher dose. The present results suggest that the receptors for TRH-elicited PRL release differ from TRH-receptors involved in its cardiovascular actions.
KW  - Neurobiologie
Y1  - 1986
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-63307
ER  - 
TY  - JOUR
A1  - Feuerstein, G.
A1  - Sirén, Anna-Leena
T1  - Effect of naloxone and morphine on survival of conscious rats after hemorrhage
N2  - The endogenous opioid system has been reported to depress the cardiovascular system during shock states, since naloxone, a potent opiate antagonist, enhances recovery of hemodynamic variables in various shock states. However, the effect of naloxone on long-term survival of experimental animals exposed to hypovolemic hypotension is not clear. The present studies tested the capacity of various doses of naloxone to protect conscious rats from mortality following various bleeding paradigms. In addition, the effect of morphine on survival of rats exposed to hemorrhage was also examined. In the six different experimental protocols tested, naloxone treatments failed to improve short- or long-term survival; in fact, naloxone treatment reduced short-term survival in two of the experimental protocols. Morphine injection, however, enhanced the mortality of rats exposed to hemorrhage in a dose-dependent manner. It is concluded that while opiates administered exogenously decrease survival after acute bleeding, naloxone has no protective action in such states and, like morphine, it may decrease survival in some situations.
KW  - Medizin
KW  - shock
KW  - opioid peptides
KW  - hypovolemic hypotension
Y1  - 1986
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-48669
ER  - 
TY  - JOUR
A1  - Feuerstein, G.
A1  - Leader, P.
A1  - Sirén, Anna-Leena
A1  - Braquet, P.
T1  - Protective effect of PAF-acether antagonist, BN 52021, in trichothecen toxicosis
N2  - Trichothecenes are mycotoxins which produce Iethai toxicosis in humans and animals, yet no adequate therapeutic regimen has been developed. This study provides evidence that the selective platelet activating factor (PAF) antagonist, BN 52021 (5-15 mg/kg i.v.) can prolong the survival of conscious rats exposed to a highly Iethai T -2 toxicosis. These data also suggest that P AF is an important mediator of this unique toxicosis.
KW  - Neurobiologie
KW  - T-2 toxin
KW  - mycotoxin
KW  - PAF-acether
KW  - BN 52021
KW  - rat
Y1  - 1987
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-63244
ER  - 
TY  - JOUR
A1  - Labroo, V. M.
A1  - Cohen, L. A.
A1  - Lozovsky, D.
A1  - Sirén, Anna-Leena
A1  - Feuerstein, G.
T1  - Dissociation of the cardiovascular and prolactin-releasing  activities of TRH by histidine replacement
N2  - No abstract available
KW  - Neurobiologie
Y1  - 1987
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-63253
ER  - 
TY  - JOUR
A1  - Feuerstein, G.
A1  - Sirén, Anna-Leena
T1  - Opioid peptides: A role in hypertension? [Brief Review]
N2  - This review is an attempt to highlight evidence that may implicate the endogenaus opioid system in the pathogenesis of hypertension in humans. The evidence raised includes biochemical, physiological, pharmacological, and behavioral studies con~ucted in in vitro andin vivo systems, experimental models of hypertension, and hornans with essential hypertension. While the compelling biochemical and pharmacological evidence in experimental animals clearly shows the presence of opioid peptides and their receptors in strategic sites of cardiovascular control and potent cardiovascular response to opioid peptides, opioid antagonists show no consistent blockade or reversal of hypertension in experimental animals or humans. One possible explanation for this phenomenon could be the vast redundancy in systems regulating blood pressure (i.e., the blockade ofone system stillleaves many other systerils fully able to rapidly offset the eliminated system). Regarding the opioid system, the situation is much more complex, since some opioid receptors (\(\mu\)-type) niediate pressor responses, while other receptors (\(\kappa\)type) mediate depressor responses. Therefore, nonselective opioid receptor antagonists (e.g., naloxone), which block both types ofreceptors, can be devoid ofany cardiovascular activity, while a selective \(\mu\)-receptor antagonist or a selective arid potent \(\kappa\)-receptor agonist may produce the desired antihypertensive elfect. A combination of both actions (i.e., a drug that is both \(\mu\)antagonist and a \(\kappa\)antagonist) might be even more advantageous. Until such compounds are developed, this hypothesis will be hard to prove.
KW  - Neurobiologie
Y1  - 1987
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-63262
ER  - 
TY  - JOUR
A1  - Feuerstein, Giora
A1  - Sirén, Anna-Leena
T1  - The Opioid System in cardiac and vascular regulation of normal and hypertensive states
N2  - The endogenous opioid system includes three major families of peptides: dynorphins (derived from pre-proenkephalin B), endorphins (derived from pre-proopiomelanocortin), and enkephalins (derived from pre-proenkephalin A). Multiple species of opioid peptides are derived from these major precursors and many of them possess potent cardiovascular properties. Opioid peptides and opioid receptors, of which multiple forms have been defined, are present in the central nervous system and peripheral neural elements. In the central nervous system, opioid peptides and receptors are found in forebrain and hindbrain nuclei involved in baroregulation, sympathoadrenal activation, and several other vital autonomic functions. In the periphery, opioid peptides are found in autonomic ganglia, adrenal gland, heart, and other organs; multiple opioid receptors are also found in vascular tissue, heart, and kidneys. Although little is known to date on the regulatory mechanisms of the opioid system in normal cardiovascular states, it became clear that cardiovascular stress situations substantially modify the activity of the endogenous opioid system. The purpose of this review is to clarify the sites of interaction of the opioid system with all major components of the cardiovascular system and indicate the potential role of this system in the ontogenesis of cardiac malfunction, vascular diseases, and hypertension.
KW  - Medizin
Y1  - 1987
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-47418
ER  - 
TY  - JOUR
A1  - Feuerstein, G.
A1  - Sirén, Anna-Leena
T1  - Cardiovascular effects of enkephalins
N2  - Enkephalins and their receptors are found in neurons and nerve terminals known to be involved in central cardiovascular control as well as the peripheral sympathetic and parasympathetic systems. Enkephalins and opioid receptors were also iden tified in the heart, kidneys, and blood vessels. The enkephalins interact with several specific receptors, of which p, 0, and K have been best characterized. Enkephalins administered to humans or animals produce cardiovascular effects which depend on the spedes, route of administration, anesthesia, and the selectivity for receptor subtype. While little information exists on the role of enkephalins in normal cardiovascular control, current data suggest that enkephalins might have a role in cardiovascular stress responses such os in shock and trauma.
KW  - Medizin
Y1  - 1987
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-49048
ER  - 
TY  - JOUR
A1  - Sirén, Anna-Leena
A1  - Feuerstein, Giera
T1  - Central autonomic pharmacology of thyrotropin releasing hormone
N2  - Thyrotropin releasing hormone (TRH, I-pyroglutamyl-l-histidyl-l-prolinamide) was the fIrst hypothalamic releasing SUbstance to be isolated, chemically characterized and synthetized /1/. The studies to date have revealed that the thyrotropin release from the pituitary gland is only one of the numerous actions of TRH. In addition to its endocrine actions (TSH and prolactin release) this tripeptide has central nervous system actions totally unrelated to its effects on the hypothalamo-pituitary axis. This review aims to summarize the studies on the central nervous system' actions of TRH with special emphasis on the autonomic pharmacology of this peptide.
KW  - Medizin
Y1  - 1987
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-49051
ER  - 
TY  - JOUR
A1  - Paakkari, I.
A1  - Sirén, Anna-Leena
A1  - Nurminen, M.-L.
A1  - Svartström-Fraser, M.
T1  - Injection of thyrotropin releasing hormone into the locus coeruleus increases blood pressure
N2  - Thyrotropin releasing hormone (TRH), 10 pmol kg-1 injected in the region of locus coeruleus, caused a rapid (within 1 min) rise of mean arterial pressure in the urethane- naesthetized rat. No clear-cut effects in heart rate or ventilation were observed. When TRH was injected into the lateral ventricle, a dose more than 10-fold higher was required to achieve a comparable rise in arterial pressure. It is concluded that TRH may have a physiological rote in centrat cardiovascular regulation.
KW  - Thyreotropin-Releasinghormon
KW  - Blutdruck
KW  - Locus coeruleus
KW  - TRH
KW  - blood pressure
KW  - locus coeruleus
Y1  - 1987
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-72894
ER  - 
TY  - JOUR
A1  - Feuerstein, G.
A1  - Letts, G.
A1  - Sirén, Anna-Leena
T1  - N-Ac-Leukotriene E\(_4\): Unique vascular activity in the conscious rat
N2  - No abstract available
KW  - Neurobiologie
Y1  - 1988
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-63171
ER  - 
TY  - JOUR
A1  - Sirén, Anna-Leena
A1  - Lake, C. R.
A1  - Feuerstein, G.
T1  - Hemodynamic and neural mechanisms of action of thyrotropin releasing hormone in the rat
N2  - Tbe mechanisms mediating the etl'ects ofthyrotropin-releasing hormone (TRH) on the cardiovascular system were studied in the conscious rat. Intracerebroventricolar (i.c. v.) injection of TRH (8 pmol-80 nmollkg) induced dose-dependent lncreases in mean arterial pressure, heart rate, and cardiac index. Rindquarter blood Oow increased due to vasodilation, while an lncrease in renal and mesenteric vascular resistance caused a decrease in blood Oow in the respective organs. The plasma Ievels of norepinephrine a~d epinephrine were increased by TRH, while there was no change in plasma renin activity or vasopressin. Tbe cardiovascular actions of i.c. v. TRH were not in.fluenced by blockade of the renin-angiotensin system or vasopressin receptors. Tbe ganglion blocker chlorisondamine and the a 1- aod al-adrenoreceptor antagooist phentolamlne (2 mg/kg i.v.) abolished the increase in blood pressure and mesenteric vasoconstriction after i.c. v. TRH. Propranolol (2 mg/kg i. v.) blocked the TRH-ioduced increase in cardiac index, heart rate, and hindquarter blood flow. The hindquarter vasodllatlon lnduced by TRH was also blocked by the selective ß1-adrenocept9r antagonist ICI 188,551 (1 or 2 mg/kg i.v.), while tbe ,8,-adrenoceptor blocker practolol (10 mg/kg i.v.) had no eft'ect on the hindquarter vasodiJation produced by TRH but totally blocked the increase in cardiac Index. In adrenal demedullated rats, the systemic hemodynamic eft'ects ofi.c. v. TRH were dimlnished along with the decrease in renal blood flow and lncrease in renal vascular resistance; however, the iocrease in hfndquarter blood flow was attenuated only in adrenal demedullated rats pretreated with the sympathetlc blocker bretylium. The renal vasoconstriction induced by i.c. v. TRH was not abolished by renal denervation. In sinoaortic debufl'ered rats, the pressor, tachycardic, and mesenteric vasoconstrictor responses to centrally administered TRH were significantly potentiated. Taken together, these data soggest that the putative rieurotransmitter TRH may play a role in central regulation of cardiac functions and organ blood flow distribution through both tbe sympathetic nerves and the adrenal medulla. A pivotal roJe for ß1-adrenoceptors in mediation ofhindquarter vasodilation ls also demonstrated.
KW  - Neurobiologie
Y1  - 1988
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-63183
ER  - 
TY  - JOUR
A1  - Sirén, Anna-Leena
A1  - Letts, G.
A1  - Feuerstein, G.
T1  - N-Acetyl-leukotriene E\(_4\) is a potent constrictor of rat mesenteric vessels
N2  - N-Acetyl-leukotriene E\(_4\) administered to conscious freely moving rats produced a dose-dependent vasoconstriction in the mesenteric vessels which led to profound reduction of blood flow to the gut. Renal and hindquarter blood flow and vascular resistance were not affected even by high doses of N-acetyl-leukotriene E\(_4\) . N-Acetyl-leukotriene E\(_4\) was 10-fold more potent than the thromboxane analog U-46619 and 1000-fold more potent than prostaglandin F\(_{2a}\) but 2-5-fold less potent than leukotriene D\(_4\)/E\(_4\) to induce mesenteric vasoconstriction. These data indicatc that N-acetylleukotriene E\(_4\) is a biologically active metabolite of peptide leukotrienes, and might play a role in cardiovascular derangements mediated by leukotrienes.
KW  - Neurobiologie
KW  - Peptide-leukotrienes
KW  - N-Acetyl-leukotriene E4
KW  - Prostaglandins
KW  - Mesenteric circulation
KW  - Anaphylactic shock
Y1  - 1988
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-63196
ER  - 
TY  - JOUR
A1  - Feuerstein, G.
A1  - Sirén, Anna-Leena
T1  - Mesenteric vascular responses to i.v. administration of lipoxin A\(_4\) and lipoxin B\(_4\) in the conscious rat
N2  - Lipoxin A (LXA\(_4\)) and lipoxin B\(_4\)(LXB\(_4\)) are newly discovered lipoxygenase-interacting products of leukocytes which might have a role in cardiovascular events associated with anaphylaxis. We have tested this possibility by systemic administration of both LXA\(_4\) and LXB\(_4\) to the conscious rat while monitaring systemic and regional hemodynamic changes. LXA\(_4\) and' LXB\(_4\) (l-100 pg/kg) produced dose-dependent constriction of the mesenteric vessels, up to + 123±23% and +50±9% for LXA\(_4\)/B\(_4\) , respectively. Dose-related changes were not observed in arterial blood pressure, heart rate, renal (LXB\(_4\)) and hindquarter blood ftow. We suggest that LXA\(_4\) and LXB\(_4\) might affect selective vascular beds, such as the mesenteric vessels, and contribute to variations in blood flow in specific pathophysiological states.
KW  - Neurobiologie
KW  - Lipoxin
KW  - Anaphylaxis
KW  - Mesenteric circulation
KW  - Renal circulation
KW  - Icosanoid
Y1  - 1988
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-63200
ER  - 
TY  - JOUR
A1  - Sirén, Anna-Leena
T1  - Cardiovascular pharmacology of thyrotropin releasing hormone
KW  - Neurobiologie
Y1  - 1988
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-63214
ER  - 
TY  - JOUR
A1  - Feuerstein, G.
A1  - Sirén, Anna-Leena
T1  - Hypothalamic µ-receptors in the cardiovascular control: a review
N2  - The endogenous opioid system includes three major families of peptides [22): dynorphins (derived from pre-proenkephalin B); endorphins (derived from pre-proopiomelanocortin) and enkephalins (derived from pre-proenkephalin A). Multiple species of opioid peptides are derived from these major precursors and many of them possess potent cardiovascular properties. Multiple forms of opioid receptors have been defined in the central nervous system. Although the relationship of these receptors to the multiple actions of the opioid systems is not weil understood, some predications can be made: in vitro the dynorphin-related peptidesbind preferentially to kappa-opioid receptors; the enkephalins bind preferentially to delta and JL-opioid receptors and while beta-endorphin binds to mu- and delta-, but not to kappa-opioid receptors. While littleis known on the roJe ofthe opioid system in normal cardiovascular regulation, it has become clear that cardiovascular stress situations substantially modify the activity ofthe endogenous opioid system. This review focuses on the mu-opioid system in the hypothalamus with special emphasis on its potential roJe in cardiovascular control of both normal and pathophysiologic states.
KW  - Neurobiologie
KW  - µ opioid receptors
KW  - Hypothalamus
KW  - Cardiovascular system
KW  - Sympathetic nervous system
Y1  - 1988
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-63228
ER  - 
TY  - JOUR
A1  - Sirén, Anna-Leena
A1  - Feuerstein, G.
T1  - Cardiovascular effects of rat calcitonin gene-related peptide in the conscious rat
KW  - Neurobiologie
Y1  - 1988
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-63236
ER  - 
TY  - JOUR
A1  - Hallenbeck, JM
A1  - Dutka, AJ
A1  - Kochanek, PM
A1  - Sirén, Anna-Leena
A1  - Pezeskpour, GH
A1  - Feuerstein, G.
T1  - Stroke risk factors prepare rat brainstem tissues for a modified localized Shwartzman reaction
N2  - Stroke risk factors such as hypertension, diabetes, advanced age, and genetic predisposition to stroke were demonstrated to prepare rat brainstem tissues for a modified local Shwartzman reaction. A single intracisternal injection of endotoxin provoked the reaction, and affected rats manifested neurologie deficits accompanied by pathologie lesions. Brainstem infarcts developed in only a small proportion of rats without recognized risk factors after intracisternal injection of endotoxin. Thus, stroke risk factors, whieh are ordinarily regarded as operating through acceleration of atherosclerosis, may predispose to brain ischemia by local effects on brain mierocirculation such as those thought to underlie preparation of a tissue for the local Shwartzman reaction.
KW  - Gehirn
KW  - Durchblutung
Y1  - 1988
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-47971
ER  - 
TY  - JOUR
A1  - Sirén, Anna-Leena
A1  - Feuerstein, G.
T1  - Effect of PAF and BN 52021 on cardiac function and regional blood flow in the conscious rat
N2  - No abstract available
KW  - Neurobiologie
Y1  - 1989
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-63145
ER  - 
TY  - JOUR
A1  - Sirén, Anna-Leena
A1  - Feuerstein, G.
T1  - Thyrotropin releasing hormone-induced hindquarter vasodilation is mediated by \(\beta _2\)-adrenoceptors
N2  - No abstract available
KW  - Neurobiologie
Y1  - 1989
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-63155
ER  - 
TY  - JOUR
A1  - Sirén, Anna-Leena
A1  - Feuerstein, G.
T1  - Hemodynamic effects of endothelin after systemic and central nervous System administration in the conscious rat
N2  - No abstract available
KW  - Neurobiologie
Y1  - 1989
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-63165
ER  - 
TY  - JOUR
A1  - Sirén, Anna-Leena
A1  - Paakkari, P.
A1  - Goldstein, D. S.
A1  - Feuerstein, G.
T1  - Mechanism of central hemodynamic and sympathetic regulation by µ-opioid receptors: Effects of dermorphin in the conscious rat
N2  - The effects of i.c.v. administered dermorphin, a highly selective \(\mu\)-opioid agonist, on cardiac function and renal, mesenteric and hindquarter blood ftow were studied in conscious rats. Core temperature, blood gases, arterial plasma levels of norepinephrine, epinephrine, dopamine, 3,4-dihydroxyphenylalanine and dihydroxyphenylacetic acid (DOPAC) also were examined. Cardiac output was rneasured using a thermodilution technique and regional blood ftows using directional pulsed Doppler velocimetry. Dermorphin, at doses of 0.1-100 nmol/kg, increased blood pressure and hindquarter blood flow, renal and mesenteric resistance, and core temperature. Higher doses (1-5 \(\mu\)mol/kg) caused respiratory depression, acidosis, and shock despite profaund sympatho-adrenomedullary stimulation. Circulating Ieveis of catecholamines were significantly increased at the dermorphin doses of 0.1-1 00 nmol/kg. At the 100 nmol/kg dose, plasma levels of epinephrine, norepinephrine, the dopamine metabellte dihydroxyphenylacetic acid and the catecholamine precursor 3,4,-dihydroxyphenylalanine were increased by 2-15-fold. The data indicate that mu opioid receptor Stimulation exerts potent effects on cardiorespiratory functions, activates the sympathoadrenomedullary system and produces a pattem of blood flow changes consistent with the stress-induced •detense· response (skeletal muscle vasodilation and splanchnic vasoconstriction). Excessive mu opioid receptor Stimulation Ieads to shock due to respiratory and hemodynamic collapse.
KW  - Neurobiologie
Y1  - 1989
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-63123
ER  - 
TY  - JOUR
A1  - Sirén, Anna-Leena
A1  - Eimerl, J.
A1  - Feuerstein, G.
T1  - L-649,923 : An antagonist of cardiac and vascular leukotriene D\(_4\) receptors
N2  - The capacity of L-649,923-sodium ( ßS, -yR * )-4-(3-( 4-acetyl-3-hydroxy-2-propylphenoxy)propylthio)-- y-hydroxy-ß-methylbenzene butanoate-to block vascular receptors of leukotriene D\(_4\) ( L TD\(_4\)) was examined in the conscious rat. Hindquarter (HQ), renal, and mesenteric blood flow and vascular resistance were evaluated in the conscious rat chronically equipped with miniaturized Doppler probes for organ blood flow measurement by directional pulsed Doppler technique. In addition, cardiac outpul was measured by thermodilution technique in conscious rats equipped with minithermistors in the ascending aorta. Systemic hemodynamic variables. mean arterial pressure, and heart rate were monitored through femoral catheters. L TD\(_4\) (I or 10 \(\mu\)g/kg) produced a marked dose dependent increase in the mesenteric vascular resistance associated with a marked decrease in blood flow whereas no consistent effects were demonstrated in the renal circulation. L TD\(_4\) • at I \(\mu\)g/kg. increased the HQ blood flow whereas the higher dose of LTD\(_4\) produced a biphasic response: an early increase followed by a decrease in blood flow. Infusion of L TD\(_4\) • 3 \(\mu\)g/kg per min over 10 min decreased cardiac output and increased total peripheral resistance. L-649,923 (10 or 30 mg/kg, i.v.) effectively blocked the L TD4-induced mesenteric constriction and the second I phase of HQ vasoconstriction but did not modify the , LTD\(_4\) induced HQ vasodilation. L-649,923 also effectively attenuated the cardiac effects of LTD\(_4\) infusion. I These studies suggest that L-649,923 could preserve cardiac and vascular functions in pathologic states mediated by cysteinylleukotrienes, such as traumatic or endotoxin shock. Key Words: Leukotriene D4 -Cardiovascular system- Leukotriene antagonist- Mesenteric blood tlow-Renal blood flow-Hindquarter blood flowAnaphylaxis.
KW  - Neurobiologie
Y1  - 1989
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-63134
ER  - 
TY  - JOUR
A1  - Feuerstein, G.
A1  - Sirén, Anna-Leena
A1  - Goldstein, DS
A1  - Johnson, AK
A1  - Zerbe, RL
T1  - The effect of morphine on the hemodynamic and neuroendocrine responses to hemorrhagic shock in conscious rats
N2  - We have previously reported that analgesic doses of morphine accelerate mortality of rats exposed to hemorrhage (Feuerstein and Siren: Circ Shock 19:293-300, 1986). To study the potential mechanisms involved in this phenomenon, rats were chronically implanted with catheters in the femoral vessels and morphine (1.5 or 5 mg/kg) was administered 30 min or 24 hr after bleeding (8.5 mll300 g over 5 min) while arterial blood pressure and heart rate were continuously monitored. Furthermore, the effect of morphine (5 mg/kg) on cardiac output (CO) response to hemorrhage was studied in rats chronically equipped with a mini thermistor for CO monitoring by a thermodilution technique. In addition, plasma catecholamines (HPLC), plasma renin activity (PRA, RIA), vasopressin (RIA), pH, and blood gases were also determined. Morphine administration 30 min after hemorrhage produced a pressor response and tachycardia which were in marked contrast to its depressor effect in intact rats. Morphine elevated PRA and epinephrine but not vasopressin, while blood pH and gases showed no consistent change as compared to salinetreated hemorrhaged rats. Morphine given after the bleeding resulted in enhanced cardiac depression in response to a second bleed of 2 m1l300 g. Our data suggest that activation of pressor mechanisms by morphine during hypovolemic hypotension might enhance vasoconstriction in essential organs, depress cardiac function, and further reduce effective tissue perfusion.
KW  - Medizin
KW  - hemorrhagic shock
KW  - opiates
KW  - catecholamlnes
KW  - renin
KW  - vasopressin
Y1  - 1989
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-49033
ER  - 
TY  - JOUR
A1  - Sirén, Anna-Leena
A1  - Feuerstein, G.
T1  - Cardiovascular effects of anatoxin-a in the conscious rat
N2  - Cardiovascular Effects of Anatoxin-A in the Conscious Rat. SJREN, A.-L., AND FEUERSTEIN, G. (1990). Toxicol. Appl. Pharmacol. 102,91-100. The effects ofanatoxin-A on mean arterial pressure (MAP), heart rate, cardiac index (CI), and blood flow (BF) in hindquarter (HQ), renal (R). and mesenteric (M) vascular beds were studied after intravenous (iv) and intracerebroventricular (icv) administration in the conscious rat. The pharmacological profile of anatoxin-A was further compared to nicotine administered iv and icv. MAP and heart rate were measured from femoral artery, CI by thermodilution method, and blood flow by Doppler velocimetry. Anatoxin-A and nicotine (30, 100 and 300 1-!g/kg iv) produced an increase in MAP with concomitant bradycardia. The highest doses increased Cl. MBF and RBF decreased due to a vasoconstriction in M and R vasculature. These effects were attenuated by the ganglion blocker chlorisondamine (5 mg/kg, iv). Anatoxin-A ( 100 1-!g/k~ iv) increased plasma epinephrine Ievels by 2- fold with virtually no effect on norepinephrine whereas nicotine ( 100 ~oLg/kg, iv) increased plasma epinephrine and norepinephrine by 20- to 30-fold. Central administration of anatoxin-A and nicotine (30-100 ,ug/kg icv) increased MAP with no effect on heart rate and produced M and R vasoconstriction. In summary, the present study demonstrates that anatoxin-A acts as a nicotinic cholinergic agonist in the c.onscious rat after both systemic and centrat administration. Anatoxin-A and nicotine produced pressor and reno-splanchnic vasoconstrictor responses and at high doses increased cardiac output. These effects were mediated by activation ofthe nicotinic receptors in the adrenal medulla and sympathetic ganglia. However, marked differences were found in the potency ofanatoxin-A versus nicotine to stimulate the sympathoadrenomedullary axis.
KW  - Neurobiologie
Y1  - 1990
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-63103
ER  - 
TY  - JOUR
A1  - Paakkari, P.
A1  - Paakkari, I.
A1  - Sirén, Anna-Leena
A1  - Feuerstein, G.
T1  - Respiratory and locomotor stimulation by low doses of dermorphin - a Mu\(_1\)-receptor mediated effect
N2  - The selective opioid mu receptor agonist dermorphin increased the locomotor activity of rats dose dependently at 1 0 to 1 00 pmol/kg i.c.v. Respiratory rate, relative tidal volume and respiratory minute volume also increased unrelated to changes in locomotor activity. Higher doses, on the other hand, produced catalepsy and respiratory depression. Pretreatment of the rats with the mu,-selective antagonist naloxonazine (10 mg/kg i.v.) blocked the stimulant locomotor and respiratory effects of low doses of dermorphin (1 0--1 00 pmol/kg), but potentiated the respiratory depressant effect of a high dose (1 0 nmol/kg) of dermorphin. The selective benzodiazepine antagonist flumazenil (5 mg/kg), which has been shown previously to antagonize catalepsy and respiratory depression produced by relatively high doses of dermorphin, did not antagonize the respiratory or locomotor stimulant effect of dermorphin. The data suggest that mu\(_1\)-opioid receptors are responsible for the low dose stimulant effects of dermorphin on locomotor activity and respiration whereas mu\(_2\) receptors mediate the respiratory depressant effect of dermorphin.
KW  - Neurobiologie
Y1  - 1990
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-63110
ER  - 
TY  - JOUR
A1  - Vonhof, S.
A1  - Sirén, Anna-Leena
A1  - Feuerstein, Giora
T1  - Volume-dependent spatial distribution of microinjected thyrotropin-releasing hormone (TRH) into the medial preoptic nucleus of the rat
N2  - The present study was performed to qua ntify the distribution of a peptide neurotransmitter after microinjection into the medial preoptic area (POM), using a technique suitable for conscious animal preparations. The results indicate that only 50-ni volumes of injected tracer were sufficiently localized with 77 ± 9% recovery in the POM. Injections of higher volumes resulted in an increasing spread of tracer into distant anatomical regions and structures, including the needle tract and cerebral ventricles. The amount of tracer localized in the POM decreased to 38±4% (200 nl) (P < 0.05) and 41 ±8% (500 nl) (P <0.05), respectively. The data suggest that the volume of injection is critical for intraparenchymal injections into structures of a diameter of I mm or less, such as the POM and should not exceed 50 nl in conscious animal preparations.
KW  - Neurophysiologie
KW  - Neurobiologie
KW  - Autoradiography
KW  - Microinjection
KW  - Hypothalamus
KW  - TRH
KW  - Neuropeptides
KW  - [3H][3Me-His2]-TRH
Y1  - 1990
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-47421
ER  - 
TY  - JOUR
A1  - Shuaib, A.
A1  - Xu, K.
A1  - Crain, B.
A1  - Sirén, Anna-Leena
A1  - Feuerstein, Giora
A1  - Hallenbeck, J.
A1  - Davis, JN
T1  - Assessment of damage from implantation of microdialysis probes in the rat hippocampus with silver degeneration staining
N2  - We used a sensitive silver degeneration staining method to study the effects of insertion of microdialysis probes in rat dorsal hippocampus and neocortex. Nine animals were sacrificed 24 h, 3 days or 7 days after implantation of dialysis tubing. Although mild neuronal cell death and small petechial hemorrhages were seen in elose proximity to the implantation site, the striking finding was the presence of degenerating axons both adjacent to the implantation site and in remote sites such as the corpus callosum and contralateral hippocampus. The observed changes could alter brain function near or remote from the implantation site and should be considered in analysis of dialysis experiments.
KW  - Neurophysiologie
KW  - Neurobiologie
KW  - In-vivo dia lysis
KW  - Silver degeneration staining
KW  - Axonal degeneration
KW  - Rat hippocampus
Y1  - 1990
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-47433
ER  - 
TY  - JOUR
A1  - Feuerstein, G.
A1  - Zerbe, R. L.
A1  - Sirén, Anna-Leena
T1  - Supraoptic nuclei in vasopressin and hemodynamic responses to hemorrhage in rats
N2  - CARDIOVASCULAR and vasopressin (A VP) responses to hcmorrhagc wcrc studicd in rats with lesions of the hypothalamic supraoptic nuclei (SONL). Bleeding caused hypotension and increase in heart rate (HR) and A VP. SONL rats failed to fully recover from bleeding as compared to normal rats. Plasma A VP in SONL rats was in the normal in basal conditions, but failed to increase to levels attained in normal rats throughout the post-hemorrhage period. These data suggcst that the supraoptic nuclei are the primary regulatory sitcs for A VP release in rcsponse to hemorrhage and that lack of adequate A VP release significantly retards blood pressure recovery after bleeding.
KW  - Neurobiologie
KW  - Hypothalamus
KW  - Supraoptic nucleus
KW  - Hemorrhage
KW  - Vasopressin
Y1  - 1991
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-63057
ER  - 
TY  - JOUR
A1  - Sirén, Anna-Leena
A1  - Feuerstein, G.
T1  - Hypothalamic opioid µ-receptors regulate discrete hemodynamic functions in the conscious rat
N2  - The effect of the selective \(\mu\)-opioid agonist o-Ala\(^2\)-Me-Phe\(^4\)-Gly-ol'-enkephalin (DAGO), injected into the medial preoptic nucleus of hypothalamus, on cardiac output and regional blood flow was studied in the conscious rat and the effect of DAGO on renal sympathetic nerve activity and renal blood flow was studied in anesthetized rats. In conscious rats, injections of DAGO (1 or 10 nmol) into the preoptic nucleus increased the blood pressure in a dose-related manner. The maximum rises of mean arterial pressure and pulse pressure after the larger dose were +23 ± 5 mmHg (mean ±SEM, P < 0.01) and + 17 ± 3 mmHg(P < 0.01), respectively. A small dose (0.1 nmol) increased heart rate ( +47 ± 13 bpm, P < 0.05); thc 1 nmol dosc produced bradycardia (- 39 ± 11 bpm, P < 0.05), while the 10 nmol dose initially decreased heart rate ( -68 ± 15 bpm (P < 0.01) and then gradually increased heart rate to a maximum of + 74 ± 13 bpm, (P < 0.0 1). A long-lasting increase in cardiac output was also elicited by DAGO, with maximum changes after 1 and 10 nmol of + 14 ± 6% and +22 ± 7% (P < 0.01), respectively. B1ood flow in the hindquarters increascd after DAGO but the mesenteric and renal blood ftow decreased in a dose-related manner. Significant responscs in hindquarter and mesenteric blood fl.ow after DAGO were independent of systemic hemodynamic responses at the dose ofO.l nmol. The vascular resistance in the hindquarters significantly decreased after a small dose of DAGO while the larger doses dose-dependently increased mesenteric and renal vascular resistance. A crucial role of the sympathetic nervous system in the hemodynamic effects of DAGO was demonstrated: (1) by the profound activation of renal sympathetic nerve activity after injections of DAGO (I nmol/100 nl) into the preoptic nucleus, (2) by blockade of the pressor, tachycardic and regional hemodynamic effects of DAGO (I nmol) by the ganglion blocker ch1orisondamine (5 mg/kg i.v.). The results suggest that the pressor effect of DAGO in preoptic nucleus is due primarily to an increase in cardiac output. The differential changes in blood ftow in organs further suggest that the opioid \(\mu\)-receptors in the preoptic nucleus might be involved in the integration of peripheral blood ftow in the hypothalamus during affective behavior.
KW  - Neurobiologie
KW  - chlorisondamine
KW  - blood pressure
KW  - heart rate
KW  - cardiac output
KW  - regional blood ftow
KW  - sympathetic nerve activity.
Y1  - 1991
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-63069
ER  - 
TY  - JOUR
A1  - Vonhof, S.
A1  - Sirén, Anna-Leena
A1  - Feuerstein, G.
T1  - Central ventilatory effects of thyrotropin-releasing hormone in the conscious rat
N2  - Thyrotropin-releasing hormonewas shown to exert potent ventilatory effects after centrat administration. These data, however, were derived from studies using anesthetized animal preparations. Since TRH elicits strong arousal reactions, the observed ventilatory effects of TRH under anesthesia may have been due to nonspecific reduction in the anesthetic state of the animals. In order to clarify the extent to which the reversal of anesthesia may change ventilatory parameters after TRH application, we investigated the effect of TRH on Ventilation rate, relative tidal volume, relative respiratory minute volume, CO\(_2\) production CO\(_2\) consumption, and locomotor activity in the conscious, unrestrained rat. Intracerebroventricular application of TRH induced a dose-dependent, sustained increase in ventilation rate, relative tidal volume, and relative respiratory minute volume of maximally 128%, 890%, and 235%, respectively. In addition, CO\(_2\) production and O\(_2\) consumption were elevated by 4.6 and 11.7 fold, whiJe no significant changes in locomotor activity were observed. The results suggest that TRH stimulates ventilation by a mechanism independent of its analeptic properties.
KW  - Neurobiologie
Y1  - 1991
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-63075
ER  - 
TY  - JOUR
A1  - Adeyemo, O. M.
A1  - Shapira, S.
A1  - Tombaccini, D.
A1  - Pollard, H.
A1  - Feuerstein, G.
A1  - Sirén, Anna-Leena
T1  - A goldfish model for evaluation of the neurotoxicit of \(\omega\)-conotoxin GVIA and screening of monoclonal antibodies
N2  - A Goldfish Model for Evaluation of the Neurotaxicity of \(\omega\)-Conotoxin GVI A and Screening of Monoclonal Antibodies. ADEYEMO, 0. M .. SHAPIRA, S., TOMBACCINI, D., POLLARD, H. 8 .• FEUERSTEIN, G .. AND SIREN, A-L. ( 1991 ). Toxicol. App/. Pharmaco/. 108, 489-496. The neurotoxicity of \(\omega\)-conotoxin (\(\omega\)-CgTx), a potent neuronal voltage-sensitive calcium channel blocker, was measured using a new bioassay. \(\omega\)-CgTx was administered intraperitoneally (ip) to goldfish weighing approximately 1.6 g, and dose-related changes were observed over a 2-hr period. \(\omega\)CgTx induced time- and dose-dependent abnormal swimming behavior (ASB) and mortality. The antitoxin activity of the antiborlies was investigated in vivo by either ( l) preincubation of the antibody with w-CgTx at 4°C overnight, or (2) pretreatment with antibody, 30 min before \(\omega\)CgTx injection in a 10:1 antibody/\(\omega\)-CgTx molar ratio. The LD50 dose of \(\omega\)-CgTx in goldfish was 5 nmol/kg ip, and preincubation of monoclonal antibody (50 nmol/kg ip) with \(\omega\)-CgTx (5 nmol/kg ip) significantly (p < 0.05) reduced mortality. ASB, and toxicity time. The antitoxin activity of the monoclonal antiborlies evidenced in the goldfish bioassay was further tested in the conscious rat. In the rat, the increases in mean arterial pressure and heart rate induced by \(\omega\)-CgTx (0.03 nmol/rat icv) were significantly (p < 0.02 and p < 0.0 l, respectively) attenuated by preincubation of the toxin with the antibody (0.3 nmol/rat). We conclude that the goldfish bioassay provides a simple. accurate, and inexpensive in vivo model for the study of the toxicity of \(\omega\)CgTx
KW  - Neurobiologie
Y1  - 1991
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-63087
ER  - 
TY  - JOUR
A1  - Sirén, Anna-Leena
A1  - Vonhof, S.
A1  - Feuerstein, G.
T1  - Hemodynamic defense response to thyrotropin-releasing
hormone injected into medial preoptic nucleus in rats
N2  - No abstract available
KW  - Neurobiologie
Y1  - 1991
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-63099
ER  - 
TY  - JOUR
A1  - Vonhof, S.
A1  - Sirén, Anna-Leena
T1  - Reversal of µ-opioid-mediated respiratory depression by α2-adrenoceptor antagonism
N2  - The present study was performed in order to evaluate the effects of the selective 02- adrenoceptor antagonist 6-chloro-2,3,4,5-tetrahydro-3-methyl-1H-3-benzazepine (SK&F 86466) on dermorphin-induced analgesia, respiratory depression and inhibition of locomotor activity in the conscious rat. Intracerebroventricular (icv) administration of dermorphin (3 nmol/rat) decreased respiration rate and relative ventilatory minute volume maximally by 38 % and 50 % of baseline respectively. SK&F 86466 dose-dependently reversed the dermorphin-induced depression of ventilatory parameters, while SK&F 86466 exerted no effect on dermorphin-induced analgesia or depression of locomotor activity due to catalepsia. It appears, therefore, that a 2-adrenoceptors selectively interact with Jl2-opioid-receptor mediated effects, such as respiratory depression, but are not involved in the modulation of Jl,-opioid-related effects, such as supraspinal analgesia and depression of locomotor activity.
KW  - Biowissenschaften
Y1  - 1991
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-47454
ER  - 
TY  - JOUR
A1  - Paakkari, P.
A1  - Paakkari, I.
A1  - Feuerstein, G.
A1  - Sirén, Anna-Leena
T1  - Evidence for differential opioid µ\(_1\)- and µ\(_2\)-receptor regulation of heart rate in the conscious rat
N2  - The possibility that \(\mu\)Opioid-induced tachycardia and bradycardia could be mediated by different subtypes of the \(\mu\)·receptor was studied in conscious Sprague-Dawley rats. The selective \(\mu\)·receptor agonist dermorphin and its analog, TAPS (Tyr-o-Arg-Phe-sarcosine), a putative \(\mu _1\)-receptor agonist, were given centrally. Tyr-o-Arg-Phe-sarcosine increased the heart rate, the response being inversely correlated to the dose (an increase of 71 ± 22, 49 ± 14 and 30 ± 17 beats/min at doses of 0.3, 3 and 30 pmol, respectively). Dermorphin induced less clear changes in heart rate (maximum increase of 39 ± 14 beats/min at the dose of 1 pmol). Aftertreatment with the Jl 1-selective antagonist naloxonazine (NAZ), TAPS 30 pmol and dennorphin I pmol decreased heart rate by -22 ± 10 and -24 ± 7 bpm, respectively. The bradycardic effect oflarger doses of dennorphin was potentiated by NAZ (from -25 ± 8 to -97 ± 22 bpm) but abolished by the non-selective antagonist naloxone. These data suggest that the high affinity \(\mu _1\)-opioid receptors mediate tachycardic responses and \(\mu _2\)-receptors mediate bradycardic responses.
KW  - Neurobiologie
KW  - dennorphin
KW  - naloxonazine
KW  - naloxone
KW  - heart rate
KW  - blood pressure
KW  - µ·Opioid receptor subtypes
Y1  - 1992
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-63017
ER  - 
TY  - JOUR
A1  - Adeyemo, M.
A1  - Sirén, Anna-Leena
T1  - Cardio-respiratory changes and mortality in the conscious rat induced by (+)- and (±)- anatoxin-a
N2  - 0. M. ADEYEMO and A.-L. SIREN. Cardio-respiratory changes and mortality in the conscious rat induced by ( + )- and ( ± )-anatoxin-a. Toxicon 30, 899-905, 1992.-Anatoxin-a (AnTx-a) isapotent nicotinic cholinergic receptor agonist. The relative potencies of the ( + )-AnTx-a and the racemic mixture ( ± )-AnTxa were investigated in the conscious rat by comparing their effects on mean arterial blood pressure (BP), heart rate (HR), blood oxygen and carbon dioxide pressures (p02 and pC02, respective1y), acid-base balance (pH) and mortality. The present experiments show that while both forms of AnTx-a produce dose-dependent increases in BP and decreases in HR, ( + )-AnTx-a is about IO-fo1d morepotent than the optically inactive isomer. ( + )-AnTx-a was also 6-fo1d more potent than ( ± )-AnTx-a in produclog severe hypoxemia, and more than 4-fold as potent as the (±}-AnTx-a in producing significant hypercapnia accompanied with severe acidosis. The approximate median Iethai dose (Ln so) of ( + )-AnTx-a was about 5-fold less than that of ( ± )-AnTx-a. We conclude that ( + )-AnTx-a is more potent than the ( ± )-AnTx-a racemic mixture in causing detrimental cardio-respiratory changes and therefore increased mortality in the rat.
KW  - Neurobiologie
Y1  - 1992
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-63027
ER  - 
TY  - JOUR
A1  - Sirén, Anna-Leena
A1  - Feuerstein, G.
T1  - The Opioid System in circulatory control
N2  - Opioid peptidesandmultiple opioid receptors are found in brain cardiovascular nuclei, autonomic ganglia, the heart, and blood vessels, and opioids induce potent cardiovascular changes. The role of endogenaus opioids in normal cardiovascular homeostasis is unclear; however, current data suggest opioid involvement in stress.
KW  - Neurobiologie
Y1  - 1992
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-63045
ER  - 
TY  - JOUR
A1  - Doron, D. A.
A1  - McCarron, D. M.
A1  - Heldman, E.
A1  - Sirén, Anna-Leena
A1  - Spatz, M.
A1  - Feuerstein, G.
A1  - Pollard, H. B.
A1  - Hallenbeck, J. M.
T1  - Comparison of stimulated tissue factor expression by brain microvascular endothelial cells from normotensive (WKY) and hypertensive (SHR) rats
N2  - The amounts of tissue factor (TF) expressed by brain microvascular endothelial cells (BMECs) from normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were compared after stimulating the cells with different doses of lipopolysaccharide (LPS), thrombin, phorbol myristic acid (PMA), Ca\(^{2+}\)·ionophore (A23187), or tumor necrosis factor (TNF) and interleukin·l (IL.l). Treatment ofcultured BMECs fron. WKY and SHR with all of these factors dose·dependently increased their total amount of TF; no substantive differences in the Ieveis of enhanced TF expression were observed between WKY and SHR BMECs. We conclude that stimulated endothelium from rats with hypertension, a major stroke risk factor, is not hyperresponsive with respect to TF expression when compared to normotensive controls.
KW  - Neurobiologie
KW  - Endothelium
KW  - Thromboplastin
KW  - Lipopolysaccharide
Y1  - 1992
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-63032
ER  - 
TY  - JOUR
A1  - Sirén, Anna-Leena
A1  - Heldman, Eliahu
A1  - Doron, David
A1  - Yue, Tian-Li
A1  - Liu, Yong
A1  - Feuerstein, G.
A1  - Hallenbeck, JM
T1  - Release of proinflammatory and prothrombbtic mediators in the brain and peripheral circulation in spontaneously hypertensive and normotensive Wistar-Kyoto rats
N2  - Background and Purpose: We reported previously that stroke risk factors prepared the brain stem for the development of ischemia and hemorrhage and induced the production of tumor necrosis factor following an intrathecal injection of Iipopolysaccharide, a prototypic monocyte-activating stimulus. This study evaluates whether blood or brain cells of hypertensive rats produce more proinflammatory and prothrombotic mediators than do blood or brain cells of normotensive rats. MethotJs: Levels of tumor necrosis factor, platelet-activating factor, 6-ketoprostaglandin F1a, and thromboxane B2 in the cerebrospinal fluid and blood of spontaneously hypertensive and normotensive Wistar-Kyoto rats were monitored before and after achallenge with Iipopolysaccharide. Results: Little or no activity from these media tors was found in the cerebrospinal fluid or blood of saline-injected control animals. Intravenous administration of Iipopolysaccharide (0.001, 0.1, and 1.8 mg/kg) produced dose-dependent increases in blood levels of all mediators in hypertensive rats. In normotensive rats the levels were less than in hypertensive rats and were not c1early dose-related. When Iipopolysaccharide was injected intracerebroventricularly, more tumor necrosis factor was measured in the cerebrospinal fluid than in the blood, suggesting local synthesis of this cytokine. Levels of tumor necrosis factor and platelet-activating factor in the cerebrospinal fluid were higher in hypertensive than in normotensive rats. The thromboxane A2/prostacyclin ratio was not aItered significantly between the two rat strains. Conclusions: It is suggested that the higher incidence of brain stem ischemia and hemorrhage after the intrathecal injection oflipopolysaccharide in hypertensive rats than in normotensive rats might be related to the higher levels of the two cytotoxic factors tumor necrosis factor and platelet-activating factor produced in response to such challenge.
KW  - Gehirn
KW  - Durchblutung
KW  - platelet-activating factor
KW  - prostacyclins
KW  - tumor necrosis factor
KW  - rats
Y1  - 1992
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-47469
ER  -