Analysis of the heart rate effects of 5-hydroxytryptamine in the cat; mediation of tachycardia by 5-HT1-like receptors.
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)
Saxena
P R
PR
Mylecharane
E J
EJ
Heiligers
J
J
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D007545:Isoproterenol / Q000494:pharmacology; D007650:Ketanserin; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013116:Spinal Cord / Q000502:physiology; D014326:Tropanes / Q000494:pharmacology; D014630:Vagus Nerve / Q000502:physiology
D010880:Piperidines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D014326:Tropanes; D012701:Serotonin; D007650:Ketanserin; D011433:Propranolol; D007545:Isoproterenol; C042253:bemesetron; D008784:Methysergide