Vascular postsynaptic effects of some 5-HT1-like receptor agonists in the pithed rat.

In pithed rats, serotonin (5-HT) raised blood pressure, an effect blocked by LY 53857, a selective 5-HT2 receptor antagonist, but not by antagonists of 5-HT1-like, 5-HT3, alpha-2, or alpha-1 receptors. 5-MeODMT also increased blood pressure, though less potently than 5-HT, and this effect was similarly blocked by LY 53857. Other serotonin receptor agonists—8-OH-DPAT, RU 24969, and TFMPP—were far less effective at raising blood pressure, while 5-CT lowered blood pressure. These results suggest that vasoconstriction from 5-HT and 5-MeODMT in pithed rats is primarily mediated by postjunctional 5-HT2 receptors, with postjunctional 5-HT1-like receptors playing little or no role.

Study at a glance

Abstract

5-HT induced an increase in blood pressure in the pithed rat which was antagonized by LY 53857 a selective 5-HT2 receptor antagonist. It was not antagonized by spiroxatrine, MDL 72222, idazoxan or AR-C 239, respectively 5-HT1-like and 5-HT3 receptor antagonists, alpha 2- and alpha 1-adrenoceptor antagonists. 5-MeODMT also induced an increase in blood pressure which was antagonized by LY 53857 but not by the other 5-HT receptor antagonists and alpha-adrenoceptor antagonists used, suggesting a 5-HT2 component in the pressor effect of 5-MeODMT. The maximal effect of 5-MeODMT was less marked than that of 5-HT. 8-OH-DPAT, RU 24969 and TFMPP were far less effective than 5-HT and 5-MeODMT to increase blood pressure. In contrast, 5-CT induced a vasodepressor effect. It is therefore suggested that the vasoconstriction induced by 5-HT and by 5-MeODMT in pithed rats could be due mainly to the selective stimulation of postjunctional 5-HT2 receptors because selective alpha 1- and alpha 2-adrenoceptor antagonists were ineffective against the vasoconstrictor effects of 5-HT and 5-MeODMT. The relative lack of effect of 8-OH-DPAT, RU 24969 and TFMPP to increase blood pressure suggested that postjunctional 5-HT1-like receptors play only a minor role - if any - in 5-HT induced vasoconstriction in the pithed rat.