Pharmacology of bucindolol in isolated canine vascular smooth muscle
Rimele, T.J.; Aarhus, L.L.; Lorenz, R.R.; Rooke, T.W.; Vanhoutte, P.M.
Journal of Pharmacology and Experimental Therapeutics 231(2): 317-325
1984
ISSN/ISBN: 0022-3565 PMID: 6149305 Document Number: 228379
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 .times. 10-10 to 1 .times. 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 .times. 10-7 M) had no effect on relaxations induced by sodium nitroprusside during contractions evoked by prostaglandin F2.alpha. 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 .times. 10-6 M caused relaxations of responses induced by various nonadrenergic agonists. Propranolol (5 .times. 10-6 M) did not alter the direct inhibitory effect the bucindolol had on contractions of coronary arteries or saphenus veins evoked by prostaglandin F2.alpha.; this inhibitory effect of bucindolol was independent of the endothelium. In superfused saphenous vein strips, previously incubated with [3H]norepinephrine, bucinolol (3 .times. 10-7 to 1 .times. 10-5 M) increased the basal efflux of [3H]norepinephrine and its [3H]metabolites. Bucindolol at 1 .times. 10-7 M inhibited prejunctional beta adrenoceptors without affecting prejunctional alpha adrenoceptors. These experiments indicate that bucinolol in decreasing orders of activity has nonselective beta adrenoceptor-antagonistic properties, has a selective alpha-1 adrenoceptor-inhibitory effect and has a nonspecific direct relaxing action on vascular smooth muscle.