Serotonin induced vasodilatation in the human forearm is antagonized by the selective 5-HT3 receptor antagonist ICS 205-930.
The role of 5-HT3 receptors in the biphasic vasodilator response to serotonin (5-hydroxytryptamine; 5-HT) was investigated in the forearm of 7 young healthy volunteers (aged 22-32 years). Single dose infusions of 5-HT (1 ng/kg/min) and of acetylcholine (ACh, 500 ng/kg/min) were administered into the brachial artery. Subsequently combined infusions of 5-HT together with the selective 5-HT3 receptor antagonist ICS 205-930 (350 and 700 ng/kg/min), and ACh together with ICS 205-930 (700 ng/kg/min) were given. After a pause of at least 1 hour the single infusions of 5-HT and ACh were repeated. Subsequently, 5-HT and ACh were infused together with atropine (100 ng/kg/min). Forearm blood flow (FBF) was measured by R-wave triggered venous occlusion plethysmography. Heart rate (HR) and i.a. blood pressure (BP) were recorded semi-continuously. None of the drugs in the doses used did induce systemic hemodynamic effects. After an initial rapid transient increase in FBF of 316 +/- 55%, 5-HT elicited a persistent increase in FBF of 90 +/- 22% (mean +/- SEM, p less than 0.05 for both). ACh induced a monophasic vasodilatation of 475 +/- 123% (p less than 0.05). Both the initial transient and the persistent dilatator response to 5-HT were attenuated by ICS 205-930 350 ng/kg/min (p = 0.057, n = 5) and 700 ng/kg/min (p less than 0.05, n = 7). The highest dose of ICS 205-930 did not significantly influence the dilatator response to ACh. Atropine abolished the ACh induced vasodilatation (p less than 0.05), but did not influence the biphasic dilatator response to 5-HT. Thus the 5-HT induced biphasic vasodilatation was antagonized by ICS 205-930, indicating that this response was mediated by 5-HT3 receptor activation. The fact that atropine did not influence the vascular response to 5-HT suggests that 5-HT did not induce vascular relaxation indirectly by the release of ACh from cholinergic nerve endings.
Blauw
G J
GJ
Department of Nephrology, University Hospital, Leiden, The Netherlands.
van Brummelen
P
P
van Zwieten
P A
PA
D000109:Acetylcholine / Q000008:administration & dosage / Q000494:pharmacology; D000328:Adult; D001285:Atropine / Q000008:administration & dosage / Q000494:pharmacology; D002799:Cholinergic Fibers / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology*; D007261:Infusions, Intra-Arterial; D008297:Male; D011985:Receptors, Serotonin / Q000145:classification; D012701:Serotonin / Q000008:administration & dosage / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000077526:Tropisetron; D014664:Vasodilation / Q000187:drug effects*
D007211:Indoles; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D012701:Serotonin; D000077526:Tropisetron; D001285:Atropine; D000109:Acetylcholine