Ethanol-induced vasoconstriction is mediated via redox-sensitive cyclo-oxygenase-dependent mechanisms

• Published in: Clinical science (1979) Vol. 118; no. 11-12; pp. 657 - 668
• Main Authors: YOGI, Alvaro, CALLERA, Glaucia E, HIPOLITO, Ulisses V, SILVA, Catiane R, TOUYZ, Rhian M, TIRAPELLI, Carlos R
• Format: Journal Article
• Language: English
• Published: London Portland Press 01.06.2010
• Subjects: Animals; Aorta - drug effects; Aorta - physiology; Biological and medical sciences; Calcium - metabolism; Cells, Cultured; Dose-Response Relationship, Drug; Endothelium, Vascular - drug effects; Endothelium, Vascular - physiology; Ethanol - pharmacology; General aspects; Male; Medical sciences; Oxidation-Reduction; Prostaglandin-Endoperoxide Synthases - physiology; Rats; Rats, Wistar; Reactive Oxygen Species - metabolism; Superoxides - metabolism; Tissue Culture Techniques; Vasoconstriction - drug effects; Vasoconstriction - physiology; Verapamil - pharmacology; Redox state; Oxidative stress; Reactive oxygen species; Oxygen; Hydrogen peroxide; Calcium; Ethanol; Enzyme; Peroxides Hydrogen; Inorganic element; Artery; Mechanism; Free radical; Oxygenase; Alcoholic beverage; Hyperoxides; Induced vasoconstriction; Blood vessel; Prostanoid; Aorta; Circulatory system; Oxidoreductases; superoxide anion
• ISSN: 0143-5221; 1470-8736
• DOI: 10.1042/CS20090352

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, 100 micromol/l], 7-nitroindazole [selective nNOS (neuronal NOS) inhibitor, 100 micromol/l], oxyhaemoglobin (NO scavenger, 10 micromol/l) and ODQ (selective inhibitor of guanylate cyclase enzyme, 1 micromol/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, 10 micromol/l), SC560 (selective COX-1 inhibitor, 1 micromol/l), AH6809 [PGF2alpha (prostaglandin F2alpha)] receptor antagonist, 10 micromol/l] or SQ29584 [PGH2(prostaglandin H2)/TXA2 (thromboxane A2) receptor antagonist, 3 micromol/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.