Mechanism of Pindolol-Induced Vasoconstriction in Isolated and Perfused Dog Coronary Arteries

[摘要] References(35)Cited-By(1)The mechanism of pindolol-induced vasoconstriction in isolated and perfused dog coronary arteries was studied. Single injections of pindolol (1-100 μg), propranolol (1-30 μg), and 5-hydroxytryptamine (5-HT, 0.001-1 μg) 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 μg): bunazosin (a selective α1-adrenergic antagonist), DG 5128 (a selective α2-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 μg, 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 μM propranolol. Methysergide (10 μg) and ketanserin (100 μg) significantly suppressed 5-HT-induced vasoconstriction. Diltiazem (100 μg, a calcium antagonist) and the incubation in Ca2+-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 μM 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 α-adrenergic receptors. The vasoconstriction induced by pindolol appears to be associated with an increase of Ca2+ influx in the smooth muscle cell membrane.

[学科分类] 药理学

[关键词] Pindolol;Coronary artery;Vasoconstriction;5-Hydroxytryptamine;Ketanserin