Studies on the vasodilator actions of bucindolol in the rat

Experiments were performed in anaesthetized rats to investigate the vasodilator actions of the beta-adrenoceptor antagonist bucindolol. Bucindolol (3 mg/kg) lowered blood pressure significantly in rats pretreated with (i) prazosin (0.4 mg/kg) (ii) prazosin (0.4 mg/kg) plus propranolol (0.5 mg/kg) or (iii) labetalol (0.5 mg/kg). Thus, a portion of the hypotensive effect of bucindolol was independent of effects on alpha- or beta-adrenoceptors. This was attributed to direct vasodilatation. In reserpinized anaesthetized rats bucindolol increased heart rate and thus had an intrinsic sympathomimetic action (ISA). The ISA was equipotent with that of isoprenaline at the 0.25 nmol/kg dose level, but declined with increasing bucindolol doses, probably due to the onset of beta-adrenoceptor blockade. An isolated perfused rat tail arteries constricted by perfusing with a high-K+ Krebs solution, bucindolol (10(-5) mol/l, 10(-4) mol/l) caused a significant reduction in perfusion pressure indicative of vasodilatation. Since the perfusate contained 10(-6) mol/l propranolol, the vasodilatation was not due to beta-adrenoceptor stimulation. These results are consistent with a direct vasodilator action of bucindolol. We suggest bucindolol lowers blood pressure by a complex mechanism involving beta-adrenoceptor blockade, alpha-adrenoceptor blockade, vasodilatation and perhaps beta 2-adrenoceptor stimulation.