The present study investigated the role of reactive oxygen species (ROS) and cyclooxygenase in ethanol-induced contraction and elevation of intracellular Ca2+ ([Ca2+]i). Vascular reactivity experiments, using standard muscle bath procedures, showed that ethanol (1 – 800 mmol/l) induced contraction in endothelium-intact (EC50: 306 ± 34 mmol/l) and denuded (EC50: 180 ± 40 mmol/l) rat aortic rings. Endothelial removal enhanced ethanol-induced contraction. Pre-incubation of intact rings with L-NAME (non selective NOS inhibitor, 100 μmol/l), 7-nitroindazole (selective nNOS inhibitor, 100 μmol/l), oxyhaemoglobin (NO scavenger, 10 μmol/l) and ODQ (selective inhibitor of guanylyl cyclase enzyme inhibitor, 1 μmol/l) increased ethanol-induced contraction. Tiron (1 mmol/l), (superoxide anion (O2-) scavenger) and catalase (300 U/ml), (hydrogen peroxide (H2O2) scavenger) reduced ethanol-induced contraction to a similar extent in both endothelium-intact and denuded rings. Similarly, indomethacin (non selective cyclooxygenase inhibitor, 10 μmol/l), SC560 (selective cyclooxygenase-1 inhibitor, 1 μmol/l), AH6809 (PGF2α receptor antagonist, 10 μmol/l) or SQ29584 (PGH2/TXA2 receptor antagonist, 3 μmol/l) inhibited ethanol-induced contraction in aortic rings with and without intact endothelium. In cultured aortic vascular smooth muscle cells (VSMCs), ethanol stimulated generation of O2- and H2O2 . Ethanol induced a transient increase in [Ca2+]i, which was significantly inhibited in VSMCs pre-exposed to tiron or indomethacin. Our data suggest that ethanol induces vasoconstriction via redox-sensitive and cyclooxygenase-dependent pathways, probably through direct effects on ROS production and Ca2+ signaling. These findings identify putative molecular mechanisms whereby ethanol, at high concentrations, influences vascular reactivity. Whether similar phenomena occur in vivo at lower concentrations of ethanol remains unclear.
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Ethanol -induced vasoconstriction is mediated via redox-sensitive, cyclooxygenase-dependent mechanisms.
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Tags: a-suggest-that, cultured-aortic, effects-on-ros, vascular-smooth, vivo-at-lower
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