Studies in the rat on bucindolol, a new antihypertensive agent with beta-adrenoceptor blocking properties

The properties of a new antihypertensive agent, bucindolol, were studied in the anaesthetized rat. When administered intravenously in the dose range 0.03 to 1.0 mg/kg, bucindolol evoked dose-related decreases in mean arterial blood pressure wtih relatively little change in heart rate. Bucindolol retained nearly 50% of its hypotensive activity after ganglionic blockage with pentolinium. When administered intravenously in a dose of 0.25 mg/kg, bucindolol caused approximately 1000-fold and 100-fold shifts to the right in the dose-response curves for isoprenaline-induced chronotropic activity and hypotensive activity, respectively. The same dose of bucindolol caused a decrease in pressor responsivity to angiotensin II, no significant change in that to noradrenaline, and an increase in that to adrenaline. Bucindolol was an effective hypotensive agent, which under the conditions of test, had relatively little effect on basal heart rate, exhibited no significant alpha-adrenoceptor blocking activity in the dose range tested, had potent beta-adrenoceptor blocking properties, and exhibited an apparent direct relaxant effect on vascular smooth muscle.