5HT3 receptor-mediated vasodilation in the human forearm.
The role of neuronal 5HT3 receptors in the vascular response induced by serotonin (5-hydroxytryptamine, 5HT) was investigated in seven healthy volunteers (aged 22-32 years). Single infusions of 5HT (1 ng/kg per min) and acetylcholine (500 ng/kg per min) were administered into the brachial artery in random order. Subsequently, 5HT and acetylcholine were administered together with the selective 5HT3 antagonist ICS 205-930 (700 ng/kg per min). After a pause of at least 1 h the single infusions of 5HT and acetylcholine were repeated. Finally, 5HT and acetylcholine were infused together with atropine (100 ng/kg per min). Forearm blood flow was measured by venous occlusion plethysmography. The heart rate and intra-arterial blood pressure were recorded semi-continuously. 5HT induced an initial transient increase in forearm blood flow (316 +/- 55%, mean +/- s.e.m., P less than 0.05), followed by persistent increase (90 +/- 22%, P less than 0.05). Acetylcholine elicited a monophasic vasodilation (delta forearm blood flow 475 +/- 123%, P less than 0.05). ICS 205-930 attenuated both the initial transient vasodilation and the persistent dilatory response to 5HT (P less than 0.05 for both), but did not significantly influence the vascular response to acetylcholine. Atropine abolished the dilator response to acetylcholine (P less than 0.05), but did not influence the biphasic vasodilation induced by 5HT. These results show that the biphasic vasodilation induced by 5HT was antagonized by ICS 205-930, indicating that this response was mediated by neuronal 5HT3-receptor activation.(ABSTRACT TRUNCATED AT 250 WORDS)
Blauw
G J
GJ
Department of Nephrology, University Hospital, Leiden, The Netherlands.
van Brummelen
P
P
Chang
P C
PC
Vermeij
P
P
van Zwieten
P A
PA
D000109:Acetylcholine / Q000502:physiology; D000328:Adult; D001132:Arm / Q000098:blood supply*; D001285:Atropine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012039:Regional Blood Flow / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology*; D013997:Time Factors; D000077526:Tropisetron; D014664:Vasodilation / Q000187:drug effects
D007211:Indoles; D011985:Receptors, Serotonin; D012701:Serotonin; D000077526:Tropisetron; D001285:Atropine; D000109:Acetylcholine