title: The hypotensive effect of trimazosin is not caused solely by alpha 1-adrenoceptor blockade.
abstract: Trimazosin is a quinazoline antihypertensive agent structurally related to the selective alpha 1-adrenoceptor blocker prazosin. Trimazosin has been shown previously to have less affinity for alpha 1-adrenoceptors than prazosin. In the present study we compared the hypotensive potency and efficacy of the two agents, and their effects on pressor responses to phenylephrine in anesthetized dogs. We also determined the effect of trimazosin administered during a maximum hypotensive response to prazosin, and of sodium nitroprusside administered after trimazosin or prazosin. Compared with prazosin, trimazosin was a less potent but more efficacious hypotensive agent. At doses which caused equal or even greater hypotensive effects than those caused by prazosin, trimazosin caused less inhibition of pressor responses to phenylephrine. When administered during a maximum hypotensive response to prazosin, trimazosin caused an additional fall in pressure. These results clearly demonstrate an additional action of trimazosin beyond blockade of alpha 1-adrenoceptors. Both trimazosin and prazosin augmented the hypotensive effect of sodium nitroprusside, but only trimazosin enhanced its relaxant effect on isolated rat aorta. Thus we conclude that in addition to alpha 1-adrenoceptor blockade, another mechanism contributes to the hypotensive effect of trimazosin, and we speculate that elevation of cyclic GMP levels in vascular smooth muscle may be related to this additional mechanism.
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D006152:Cyclic GMP / Q000378:metabolism; D004285:Dogs; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology; D011311:Pressoreceptors / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects
chemical_list: D000317:Adrenergic alpha-Antagonists; D000959:Antihypertensive Agents; D010879:Piperazines; D011942:Receptors, Adrenergic, alpha; D009599:Nitroprusside; D010656:Phenylephrine; C005185:trimazosin; D006152:Cyclic GMP; D011224:Prazosin