Abstract
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 (2×10-8 moles/kg i.v.) of all drugs except phenoxybenzamine. The order of maximal fall of diastolic blood pressure after the injection was; nitroglycerin>E-643>phentolamine>verapamil>phenoxy-benzamine. Although “adrenaline reversal” was observed after 2×10-7 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 2×10-6 M inhibited the Ca-contracture (phasic and tonic) of the depolarized aortic strips. The order of inhibition of phasic and tonic contracture was: nitroglycerin> E-643, verapamil>phentolamine>phenoxybenzamine. The pA2 values for phentol-amine 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 phenoxy-benzamine), paralleled 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.
