Human Aortic Smooth Muscle Cells Containing Angiotensin II Type 1 Receptors

Abstract

ABSTRACT-The mechanism of pindolol-induced vasoconstriction in isolated and perfused dog coronary arteries was studied. Single injections of pindolol (1-100 ,ug), propranolol (1-30 pg), and 5-hydroxytryp tamine (5-HT, 0.001-1 ,ug) produced a dose-related vasoconstriction in dog coronary arteries which were dilated by acetylcholine. 1-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 rig): bunazosin (a selec tive a,-adrenergic antagonist), DG 5128 (a selective a2-adrenergic antagonist), atropine (a muscarinic an tagonist), chlorpheniramine (a selective H,-antagonist), cimetidine (a selective H2-antagonist), and ketanserin (a selective 5-HT2 antagonist). Methysergide (10 ttg, a 5-HT, and 5-HT2 antagonist) significantly reduced pindolol and propranolol-induced vasoconstrictions, although it did not reduce norepinephrine-in duced vasoconstriction in the presence of 5 iM propranolol. Methysergide (10 ,ug) and ketanserin (100 rig) significantly suppressed 5-HT-induced vasoconstriction. Diltiazem (100 pg, a calcium antagonist) and the in cubation 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 uM ketanserine. In a solution containing 20 mM KC1, 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-HT,-like receptors, but not through a-adrenergic receptors. The vasoconstriction induced by pindolol appears to be associated with an increase of Ca 21 influx in the smooth muscle cell membrane.

Characterization of 5‐hydroxytryptamine receptors mediating contractions in basilar arteries from stroke‐prone spontaneously hypertensive rats

“…P-Adrenoceptor blocking agents such as pindolol and propranolol are widely used as 5-HTlA and 5-HTIB receptor antagonists in in vitro vessel studies. However, pindolol and propranolol have also been demonstrated to cause vasoconstrictions through activation of 5-HT,-like receptors (Nakane et al, 1993). In addition, pindolol and propranolol have been shown to behave as partial or full agonists at the 5-HTlB receptors (Unsworth & Molinoff, 1992;Adham et al, 1993), and to behave as partial agonists at 5-HTID receptors (Schoeffter & Hoyer, 1989b).…”