Pharmacology of bucindolol in isolated canine vascular smooth muscle

To determine the effects of bucindolol on isolated vascular smooth muscle, rings of canine coronary and femoral arteries and saphenous veins were suspended for isometric tension recording in organ chambers filled with physiological salt solution. Bucindolol (3 x 10^-10 to 1 x 10^-7 M) had a comparable inhibitory effect on relaxations induced by isoproterenol in coronary arteries (which contain postjunctional beta-1 adrenoceptors) and saphenous veins (which contain postjunctional beta-2 adrenoceptors). Bucindolol (1 x 10^-7 M) had no effect on relaxations induced by sodium nitroprusside during contractions evoked by prostaglandin F(2α), in either saphenous veins or coronary arteries. Bucindolol also had weak (relative to its beta adrenoceptor effect) alpha adrenoceptor-antagonistic activity that was greater for postjunctional alpha-1 than alpha-2 adrenoceptors. In all tissues tested, bucindolol in concentrations greater than 1 x 10^-6 M caused relaxations of responses induced by various noradrenergic agonists. Propranolol (5 x 10^-6 M) did not alter the direct inhibitory effect that bucindolol had on contractions of coronary arteries or saphenous veins evoked by prostaglandin F(2α); this inhibitory effect of bucindolol was independent of the endothelium. In superfused saphenous vein strips, previously incubated with [³H]epinephrine, bucindolol (3 x 10^-7 to 1 x 10^-5 M) increased the basal efflux of [³H]norepinephrine and its [³H] metabolites. Bucindolol at 1 x 10^-7 M inhibited prejunctional beta adrenoceptors without affecting prejunctional alpha adrenoceptors. These experiments indicate that bucindolol in decreasing orders of activity 1) has nonselective beta adrenoceptor-antagonistic properties, 2) has a selective alpha-1 adrenoceptor-inhibitory effect and 3) has a nonspecific direct relaxing action on vascular smooth muscle.