The present study investigated the role of ROS (reactive oxygen species) and COX (cyclo-oxygenase) in ethanol-induced contraction and elevation of [Ca2+]i (intracellular [Ca2+]). 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 endothelium -denuded (EC50: 180±40 mmol/l) rat aortic rings. Endothelial removal enhanced ethanol-induced contraction. Preincubation of intact rings with L-NAME [NG-nitro-L-arginine methyl ester; non-selective NOS (NO synthase) inhibitor, 100μmol/l], 7-nitroindazole [selective nNOS (neuronal NOS) inhibitor, 100μmol/l], oxyhaemoglobin (NO scavenger, 10μmol/l) and ODQ (selective inhibitor of guanylate cyclase enzyme, 1μmol/l) increased ethanol-induced contraction. Tiron [O2− (superoxide anion) scavenger, 1 mmol/l] and catalase (H2O2 scavenger, 300 units/ml) reduced ethanol-induced contraction to a similar extent in both endothelium-intact and denuded rings. Similarly, indomethacin (non-selective COX inhibitor, 10μmol/l), SC560 (selective COX-1 inhibitor, 1μmol/l), AH6809 [PGF2α (prostaglandin F2α)] receptor antagonist, 10μmol/l] or SQ29584 [PGH2(prostaglandin H2)/TXA2 (thromboxane A2) receptor antagonist, 3μmol/l] inhibited ethanol-induced contraction in aortic rings with and without intact endothelium. In cultured aortic VSMCs (vascular smooth muscle cells), 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 COX-dependent pathways, probably through direct effects on ROS production and Ca2+ signalling. 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.
Ethanol-induced vasoconstriction is mediated via redox-sensitive cyclo-oxygenase-dependent mechanisms
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Alvaro Yogi, Glaucia E. Callera, Ulisses V. Hipólito, Catiane R. Silva, Rhian M. Touyz, Carlos R. Tirapelli; Ethanol-induced vasoconstriction is mediated via redox-sensitive cyclo-oxygenase-dependent mechanisms. Clin Sci (Lond) 1 June 2010; 118 (11): 657–668. doi: https://doi.org/10.1042/CS20090352
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