The vasopressor response to serotonin (5-HT) in rats; its dependency upon extracellular calcium.
In pithed rats it was investigated whether the serotonin-induced vasopressor response is affected by calcium entry blockers. Both verapamil isomers dose-dependently inhibited the hypertensive response to i.v. serotonin, (-)-verapamil being about 10 times more potent. Flunarazine (3 mg/kg) and the dihydropyridine derivatives, nimodipine (0.3 mg/kg) and PY-108-068 (0.3 mg/kg) as well as Na2-EDTA (120 mg/kg) were found ineffective. The doses of the calcium entry blockers and Na2-EDTA used cause a 70% reduction of the alpha 2-adrenoceptor-mediated vasopressor response in this model. In the isolated Tyrode-perfused hindquarters of the rat the flow reduction induced by serotonin is not altered by addition of 10(-7) M of PY-108-068 or by the deletion of calcium from the perfusion fluid. The results indicate that an influx of extracellular calcium is not necessarily a prerequisite for the serotonin-induced constriction of the vessels which determines the peripheral vascular resistance or the reduction of flow. Both verapamil isomers displayed a considerable affinity for rat brain 5-HT2 receptors (identified by [3H]mianserin). It therefore seems likely that verapamil inhibits serotonin-induced vasopressor responses on the basis of a genuine receptor-antagonism.
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects*; D001921:Brain / Q000378:metabolism; D002118:Calcium / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004492:Edetic Acid / Q000494:pharmacology; D006614:Hindlimb / Q000098:blood supply; D066298:In Vitro Techniques; D008297:Male; D008803:Mianserin / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects; D012039:Regional Blood Flow / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects
D002121:Calcium Channel Blockers; D011985:Receptors, Serotonin; D008803:Mianserin; D012701:Serotonin; D004492:Edetic Acid; D002118:Calcium