Pirkko Paakkari

Further evidence for central histamine H2-receptor involvement in the hypotensive effect of clonidine in the rat.

In urethane-anaesthetised rats, the administration of the specific histamine H2-receptor antagonist metiamide intracerebroventricularly (i.c.v.) raised the blood pressure and increased the heart rate. Metiamide (i.c.v.) antagonised the hypotensive effect of clonidine (i.c.v.) in an apparently competitive manner. 4-Methylhistamine i.c.v. did not significantly change the blood pressure. The results are consistent with the concept that the hypotensive effect of clonidine is at least partly due to a stimulation of cerebral H2-receptors. The existence of cerebral H2-receptors mediating hypotensive effects is supported by the hypertensive effect of metiamide but not by the lack of hypotensive effects of 4-methylhistamine.

Central hypotensive effects of imidazole acetic acid and rolipram (ZK 62 711) in rats

In urethane-anaesthetized rats the administration of imidazole acetic acid (IAA), 34–272 μg per rat intracerebroventricularly (i.c.v.), induced a dose-related fall in blood pressure. Rolipram (ZK 62 711), a potent and selective inhibitor of cyclic AMP phosphodiesterase (cAMP-PDE), also lowered the blood pressure in a dose-dependent manner when administered at the doses of 1–64 μg per rat i.c.v. A subhypotensive dose of rolipram (0.25 μg per rat i.c.v.) did not change the hypotensive effect of IAA. Pretreatment of the rats with metiamide, 1.1. mg per rat i.c.v., shifted the dose-response curve for IAA significantly to the right. The present results make it unlikely that the central hypotensive effect of IAA could be due to the stimulation of cAMP-PDE by this agent. Central histamine H2-receptors may be involved in the hypotensive effect of IAA.