Mechanisms involved in the vasodilator action of 5-hydroxytryptamine in the dog femoral arterial circulation in vivo.
The possibility that the vasodilator effect of 5-hydroxytryptamine (5-HT) in vivo involves a presynaptic inhibitory effect on sympathetic nerve activity was investigated in the femoral arterial circulation of pentobarbitone-anaesthetized dogs. The vasodilator effect of intraarterial (i.a.) 5-HT was abolished following ganglion blockade with mecamylamine, and remained inhibited after restoration of femoral vascular tone with i.a. ornipressin. These procedures had no effect on the vasodilator response to i.a. acetylcholine. The vasoconstrictor response to i.a. noradrenaline was not inhibited by mecamylamine. These findings suggest that a presynaptic inhibition of sympathetic neurotransmission is responsible for 5-HT-induced vasodilatation in vivo. Pizotifen (0.1-0.4 mg/kg i.v.) inhibited the 5-HT dilator response, but the doses required were too high to be commensurate with an action at 'D' type 5-HT receptors. Ketanserin (0.1-0.4 mg/kg i.v.) specifically inhibited the dilator response to 5-HT; higher doses (1-4 mg/kg i.v.) also inhibited noradrenaline-induced vasoconstriction. Ketanserin, at all doses used, reduced systemic blood pressure and femoral vascular resistance. The effects of the lower doses of ketanserin (0.1-0.4 mg/kg) cannot be due to peripheral alpha-adrenoceptor antagonism; blockade of the dilator effect of 5-HT may simply be due to inhibition of sympathetic nerve activity by ketanserin itself.
Phillips
C A
CA
Mylecharane
E J
EJ
Shaw
J
J
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002245:Carbon Dioxide / Q000378:metabolism; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D005263:Femoral Artery / Q000187:drug effects*; D006614:Hindlimb / Q000098:blood supply; D007650:Ketanserin; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009951:Ornipressin / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D010918:Pizotyline / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology*; D013564:Sympathetic Nervous System / Q000502:physiology; D014665:Vasodilator Agents
D010880:Piperidines; D014665:Vasodilator Agents; D010918:Pizotyline; D002245:Carbon Dioxide; D009951:Ornipressin; D012701:Serotonin; D007650:Ketanserin