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

Yogi, A., Callera, G.E., Hipólito, U.V., Silva, C.R., Touyz, R.M. and Tirapelli, C.R. (2010) Ethanol-induced vasoconstriction is mediated via redox-sensitive cyclo-oxygenase-dependent mechanisms. Clinical Science, 118(11), pp. 657-668. (doi: 10.1042/CS20090352)

Full text not currently available from Enlighten.

Publisher's URL: http://dx.doi.org/10.1042/CS20090352

Abstract

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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Touyz, Professor Rhian
Authors: Yogi, A., Callera, G.E., Hipólito, U.V., Silva, C.R., Touyz, R.M., and Tirapelli, C.R.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Clinical Science
ISSN:0143-5221
ISSN (Online):1470-8736
Published Online:03 December 2009

University Staff: Request a correction | Enlighten Editors: Update this record