Interaction between 5-hydroxytryptamine and other vasoconstrictor substances in the isolated femoral artery of the rabbit; effect of ketanserin (R 41 468).
Experiments were designed to determine whether or not ketanserin (R 41 468) antagonizes the augmentation by 5-hydroxytryptamine of contractions evoked in isolated arteries by non-adrenergic vasoconstrictor substances. Rings of rabbit femoral arteries were studied under isometric conditions in organ chambers filled with Krebs-Henseleit solution (37 degrees C). Ketanserin, unlike methysergide and LSD, was devoid of agonistic properties. It competitively antagonized contractile responses to 5-hydroxytryptamine and, at higher concentrations, to histamine. 5-Hydroxytryptamine amplified the contractions evoked by threshold concentrations of histamine, angiotensin II and prostaglandin F2 alpha; in all three cases, the amplification was antagonized by comparable concentrations of ketanserin. These experiments indicate that the interaction of 5-hydroxytryptamine with S2-receptors of the vascular smooth muscle cells is essential to allow the expression of the monoamine-induced amplification of the response to other vasoconstrictor substances. The inhibition by ketanserin of the amplifying effect of 5-hydroxytryptamine on vascular responses may help explain the antihypertensive properties of the compound.
D000818:Animals; D004347:Drug Interactions; D005071:Evoked Potentials / Q000187:drug effects; D005263:Femoral Artery / Q000187:drug effects; D066298:In Vitro Techniques; D007650:Ketanserin; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010880:Piperidines / Q000494:pharmacology*; D011817:Rabbits; D012701:Serotonin / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D010880:Piperidines; D014662:Vasoconstrictor Agents; D012701:Serotonin; D007650:Ketanserin