Antihypertensive actions of an isomer of labetalol and other vasodilator-beta-adrenoceptor blockers.

Combinations of beta-adrenoceptor blockers and vasodilators have proved highly useful in antihypertensive therapy. Studies of the mechanisms of action of several agents that combine these effects within a single molecule are described in this report. Labetalol, SCH 19927, sulfinalol, MK-761, pindolol, and prizidilol, in contrast to propranolol, decreased blood pressure of spontaneously hypertensive rats (SHR). All except labetalol and SCH 19927 increased heart rate. In anesthetized dogs, all of these agents (except propranolol) produced vasodilatation on intra-arterial administration into the femoral vascular bed and, given i.v., lowered blood pressure after ganglionic blockade. In contrast to the other agents, labetalol and SCH 19927 caused only minimal increases in heart rate in ganglionically blocked dogs. The vasodilator and hypotensive actions as well as the antihypertensive effect in SHR of labetalol, SCH 19927, sulfinalol, and pindolol were inhibited by propranolol pretreatment but those of prizidilol were not, suggesting that the hypotensive and vascular effects of labetalol, SCH 19927, sulfinalol, pindolol, and MK-761 are mediated by activation of vascular beta-receptors. However, labetalol and SCH 19927 in particular differ from agents of this class as well as other beta blockers with strong intrinsic sympathomimetic actions in that their agonist activity is primarily directed at blood vessels and not the heart.