Analysis of the heart rate effects of 5-hydroxytryptamine in the cat; mediation of tachycardia by 5-HT1-like receptors

Abstract

The effects of 5-hydroxytryptamine (5-HT) on heart rate in anaesthetized cats were analysed both in intact animals and after spinal section plus vagotomy. The intact cat responded to 5-HT (3, 10 and 30 micrograms X kg-1, i.v.) with a brief, but intense, bradycardia and a longer-lasting hypotension. Administration of MDL 72222, a selective antagonist of M-type 5-HT receptors, blocked bradycardia elicited by 5-HT without affecting that caused by stimulation of the vagus nerve. In spinal cats the same doses of 5-HT increased heart rate and blood pressure. These effects remained essentially unchanged after bilateral adrenalectomy, guanethidine, propranolol and burimamide, suggesting that 5-HT acted directly on the myocardium and blood vessels. The tachycardic responses to 5-HT in spinal cats were little affected by 0.5 mg X kg-1 doses of MDL 72222 or of the 5-HT2 receptor antagonists, ketanserin, ritanserin or cyproheptadine. In contrast, the non-selective 5-HT receptor antagonist, methysergide, which binds to both 5-HT1 and 5-HT2 recognition sites in rat brain membranes, potently antagonized the 5-HT-induced tachycardia in doses of 0.05 to 0.5 mg X kg-1. However pizotifen and mianserin, two other 5-HT2 antagonists which show poor affinity for 5-HT1 recognition sites, were also effective against the tachycardic response to 5-HT in doses of 0.5-4.5 mg X kg-1. The pressor responses to 5-HT in the spinal cat were markedly inhibited by all six 5-HT2 antagonists at a dose of 0.5 mg X kg-1.(ABSTRACT TRUNCATED AT 250 WORDS)