Systemic hemodynamic effects of bethanidine in essential hypertension

Although available elsewhere, bethanidine remains under study in the U.S. and its hemodynamic effects are unreported. Therefore, 29 patients with moderately severe essential hypertension received one of four oral dose levels (0.10, 0.25, 0.35, or 0.50 mg/kg) of the postganglionic sympatholytic drug. Blood pressure was reduced only in the 14 patients receiving the highest dose. This was demonstrated within three hours, first by a significant postural hypotension (upright tilt: +14 before vs -19 mm Hg after, P less than 0.001). This orthostatic hypotension effect was associated with a greater fall in cardiac output (13 vs 22%, P less than 0.025) and a diminished reflective increase in total peripheral resistance (19 vs 6%, P less than 0.01); an attenuated Valsalva maneuver overshoot in the supine position was also observed (42 vs 10%, P less than 0.001). Eight of these 14 patients demonstrated supine hypotension associated with either reduced output and/or resistance. Hence, bethanidine is a rather rapidly acting oral sympatholytic agent which reduces blood pressure by producing: (1) decreasec venous return (especially in upright position), suggesting venodilation; (2) arteriolar dilation (supine and upright) reducing peripheral vascular resistance; and (3) attenuated cardiovascular sympathetic reflective adjustments.