Mechanism of pindolol-induced vasoconstriction in isolated and perfused dog coronary arteries.

The mechanism of pindolol-induced vasoconstriction in isolated and perfused dog coronary arteries was studied. Single injections of pindolol (1-100 micrograms), propranolol (1-30 micrograms), and 5-hydroxytryptamine (5-HT, 0.001-1 microgram) produced a dose-related vasoconstriction in dog coronary arteries which were dilated by acetylcholine. l-Pindolol constricted coronary arteries, but d-pindolol did not. The responses to pindolol and propranolol were not affected by any of the following compounds (100 micrograms): bunazosin (a selective alpha 1-adrenergic antagonist), DG 5128 (a selective alpha 2-adrenergic antagonist), atropine (a muscarinic antagonist), chlorpheniramine (a selective H1-antagonist), cimetidine (a selective H2-antagonist), and ketanserin (a selective 5-HT2 antagonist). Methysergide (10 micrograms, a 5-HT1 and 5-HT2 antagonist) significantly reduced pindolol- and propranolol-induced vasoconstrictions, although it did not reduce norepinephrine-induced vasoconstriction in the presence of 5 microM propranolol. Methysergide (10 micrograms) and ketanserin (100 micrograms) significantly suppressed 5-HT-induced vasoconstriction. Diltiazem (100 micrograms, a calcium antagonist) and the incubation in Ca(2+)-free solution containing 1 mM EGTA for 1 hr significantly reduced the vasoconstrictions induced by pindolol and propranolol. The Ca(2+)-free solution containing 1 mM EGTA abolished the vasoconstriction induced by 5-HT in the presence of 1 microM ketanserine. In a solution containing 20 mM KCl, the vasoconstrictions caused by pindolol and propranolol were enhanced in dog coronary arteries. These results indicate that the direct contractile effects of pindolol on dog coronary arteries are mediated, at least partly, through 5-HT1-like receptors, but not through alpha-adrenergic receptors.(ABSTRACT TRUNCATED AT 250 WORDS)