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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - Frerichs, K. A1 - Sirèn, Anna-Leena A1 - Feuerstein, G. A1 - Hallenbeck, JM T1 - The onset of postischemic hypoperfusion in rats is precipitous and may be controlled by local neurons N2 - Background and Purpose: Reperfusion following transient global cerebral ischemia is characterized by an initial hyperemic phase, which precedes hypo perfusion. The pathogenesis of these flow derangements remains obscure. Our study investigates the dynamics of postischemic cerebral blood flow changes, with particular attention to the role of local neurons. Metho(Js: We assessed local cortical blood flow continuously by laser Doppler flowmetry to permit observation of any rapid flow changes after forebrain ischemia induced by four-vessel occlusion for 20 minutes in rats. To investigate the role of local cortical neurons in the regulation of any blood flow fluctuations, five rats received intracortical microinjections of a neurotoxin (10 p,g ibotenic acid in 1 p,1; 1.5-mm-depth parietal cortex) 24 hours before ischemia to induce selective and localized neuronal depletion in an area corresponding to the sampie volume of the laser Doppler probe (1 mm3 ). Local cerebral blood flow was measured within the injection site and at an adjacent control site. Results: Ischemia was followed by marked hyperemia (235 ±23% of control, n =7), followed by secondary hypoperfusion (45±3% of control, n=7). The transition from hyperemia to hypoperfusioo occurred not gradually but precipitously (maximal slope of flow decay: 66±6%/min; n=7). In ibotenic acid-injected rats, hyperemia was preserved at the injection site, but the sudden decline of blood flow was abolished (maximal slope of flow decay: 5±3%/min compared with 53±8%/min at the control site; n=5, p