Local hemodynamic effects of serotonin and ketanserin in healthy subjects: studies in the forearm.
The vascular effects of serotonin and the selective 5-HT2 antagonist ketanserin were investigated in the forearm of healthy subjects. The drugs were infused into the brachial artery in doses that did not elicit systemic hemodynamic effects (0.1-80 ng/kg/min for serotonin and 5-125 ng/kg/min for ketanserin). The interaction between serotonin and ketanserin was studied by combined infusions of serotonin with ketanserin, and the relative 5-HT2 and alpha 1-adrenoceptor blocking potencies of ketanserin were studied by simultaneous infusions of the selective alpha 1-agonist methoxamine, the indirect sympathomimetic drug tyramine, and serotonin with two doses of ketanserin. Forearm blood flow (FBF) was measured by venous occlusion plethysmography. Heart rate and intra-arterial blood pressure were recorded continuously. All doses of serotonin induced an initial transient vasodilation that was followed by a steady vasodilation for the lower doses (0.1-10 ng/kg/min) and a steady vasoconstriction for the highest dose of serotonin (p less than 0.05). Ketanserin induced a dose-dependent vasodilation, which was significant from the dose of 15 ng/kg/min (p less than 0.05). The vasodilation induced by serotonin (1 ng/kg/min) was significantly enhanced by ketanserin, whereas the vasoconstriction elicited by serotonin of 80 ng/kg/min was reversed by ketanserin (p less than 0.05). The vasoconstriction induced by methoxamine and tyramine was attenuated at a lower dose of ketanserin than the vascular response induced by serotonin. It is concluded that serotonin acts mainly as a vasodilatator in healthy subjects, whereas only at very high doses is vasoconstriction mediated by 5-HT2 receptors observed. The vasodilation induced by ketanserin is most likely due to its alpha 1-adrenoceptor blocking potencies.
Blauw
G J
GJ
Department of Nephrology, University Hospital of Leiden, The Netherlands.
van Brummelen
P
P
Bruning
T
T
van Zwieten
P A
PA
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005542:Forearm / Q000098:blood supply*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007650:Ketanserin / Q000494:pharmacology*; D008729:Methoxamine / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; 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
D009599:Nitroprusside; D012701:Serotonin; D007650:Ketanserin; D008729:Methoxamine; D014439:Tyramine