Effects of alpha blockers on blood pressure and on the Ca-contracture of cat aortic strips.
To further clarify the hypotensive mechanism of adrenergic alpha blockers, effects of several alpha blockers on systemic blood pressure and on Ca-contracture of isolated, cat aortic strips were studied. For this purpose, the effects of known adrenergic alpha blockers, phentolamine, phenoxybenzamine, and a newly synthesized adrenergic alpha blocker (2-(N-(n-Butyloyl)homopiperazine-N'-yl)-4-amino-6,7-dimethoxy quinazoline; E-643) were compared with those of nitroglycerin and verapamil. Systemic blood pressure was decreased by administration (2 x 10(-8) moles/kg i.v.) of all drugs except phenoxybenzamine. The order of maximal fall of diastolic blood pressure after the injection was; nitroglycerin greater than E-643 greater than phentolamine greater than verapamil greater than phenoxybenzamine. Although "adrenaline reversal" was observed  after 2 x 10(-7) moles/kg of phenoxybenzamine, i.e. a 10-fold increase in the dose of phenoxybenzamine, there was no decrease in systemic blood pressure with this dose. All these drugs in a concentration of 2 x 10(-6) M inhibited the Ca-contracture (phasic and tonic) of the depolarized aortic strips. The order of inhibition of phasic and tonic contracture was: nitroglycerin greater than E-643, verapamil greater than phentolamine greater than phenoxybenzamine. The pA2 values for phentolamine and E-643 in antagonizing contractions produced by noradrenaline of cat aortic strips were 7.8 and 8.2, respectively. Hypotensive effects of these drugs (except phenoxybenzamine), parallel the inhibitory effects on the Ca-contracture  of the aortic strips. These results suggest that alpha blockers such as phentolamine and E-643 exert a systemic hypotensive effect not through their alpha blocking action but by an inhibitory action on the contractile Ca-mechanism.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects*; D002118:Calcium / Q000037:antagonists & inhibitors / Q000502:physiology; D002415:Cats; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000037:antagonists & inhibitors; D010643:Phenoxybenzamine / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects
D000317:Adrenergic alpha-Antagonists; D011799:Quinazolines; D010643:Phenoxybenzamine; C018176:bunazosin; D002118:Calcium; D009638:Norepinephrine; D010646:Phentolamine