Regional vascular effects of serotonin and ketanserin in young, healthy subjects.
The local hemodynamic effects of serotonin (5-hydroxytryptamine; 5-HT) and the selective 5-HT2 antagonist ketanserin were investigated in the forearm of 20 healthy volunteers. Single doses of 5-HT (0.1-80 ng/kg/min) and ketanserin (5-125 ng/kg/min) were administered intra-arterially. The relative alpha 1-adrenergic receptor and 5-HT2 blocking potencies of ketanserin were investigated using intra-arterial infusions of cumulative doses of methoxamine (0.1, 0.3, and 0.5 microgram/kg/min), tyramine (0.25, 0.50, and 1.25 microgram/kg/min), and 5-HT (10, 30, and 80 ng/kg/min) together with a low dose (5 ng/kg/min) and a high dose (50 ng/kg/min) of ketanserin. Forearm blood flow was measured by venous occlusion plethysmography. Heart rate and intra-arterial blood pressure were recorded semicontinuously. Intra-arterial infusion of 5-HT induced an initial transient vasodilatation, followed by a steady vasodilatation for the low doses of 5-HT (0.1-10 ng/kg/min; p less than 0.05). A steady vasoconstriction was only obtained at the highest dose of 5-HT. Ketanserin induced a dose-dependent increase in forearm blood flow from 15 ng/kg/min (p less than 0.05) onward. The vasodilatation induced by 5-HT (1 ng/kg/min) was significantly enhanced by ketanserin (125 ng/kg/min; p less than 0.05), whereas the vasoconstriction elicited by 5-HT (80 ng/kg/min) was reversed by ketanserin (50 ng/kg/min; p less than 0.05), thus confirming that 5-HT2 receptors were stimulated by 5-HT.(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
D000328:Adult; D005542:Forearm / Q000098:blood supply*; D006801:Humans; D007650:Ketanserin / Q000494:pharmacology*; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects; D012039:Regional Blood Flow / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology*; D014439:Tyramine / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*
D011942:Receptors, Adrenergic, alpha; D011985:Receptors, Serotonin; D012701:Serotonin; D007650:Ketanserin; D011433:Propranolol; D008729:Methoxamine; D014439:Tyramine