Anna-Leena Sirén

• 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 toProstacyclin (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.…