Further evaluation of the selectivity of a novel antihypertensive agent, SGB-1534, for peripheral alpha 1-adrenoceptors in the spinally anesthetized dog.

Experiments were designed to examine some characteristics of an orally active antihypertensive agent, SGB-1534 on alpha-adrenoceptors in spinally anesthetized dogs. In the saphenous arterial bed perfused by a constant pump volume, saphenous nerve stimulation and bolus applications of norepinephrine and phenylephrine into the artery-evoked frequency- or dose-dependent increases (i.e. vasoconstriction) in perfusion pressure. SGB-1534 and prazosin infused i.v. significantly reduced the vasoconstriction in response to saphenous nerve stimulation and the two agonists. In the saphenous arterial bed, alpha 1-adrenoceptor antagonist potency of SGB-1534 on a weight basis was approximately 30 times greater than that of prazosin. Unlike SGB-1534 and prazosin, yohimbine failed to inhibit the vasoconstriction induced by phenylephrine, but instead potentiated the vasoconstrictor response to saphenous nerve stimulation. The equieffective doses of methoxamine and B-HT 920 given i.v. produced sustained pressor responses. SGB-1534 and prazosin applied i.v. in a cumulative way reduced dose dependently the pressor response to methoxamine but not that to B-HT 920. When the doses that blunted the sustained pressor response to methoxamine by 50% were compared, the alpha 1-adrenoceptor antagonistic activity of SGB-1534 was nine times greater than that of prazosin.