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.
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Research Article|
March 09 2010
Ethanol-induced vasoconstriction is mediated via redox-sensitive cyclo-oxygenase-dependent mechanisms
Alvaro Yogi;
Alvaro Yogi
*Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa, Ontario, Canada
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Glaucia E. Callera;
Glaucia E. Callera
*Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa, Ontario, Canada
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Ulisses V. Hipólito;
Ulisses V. Hipólito
†Department of Pharmacology, Faculty of Medicine of Ribeirão Preto, University of São Paulo (USP), SP, Brazil
‡Department of Psychiatric Nursing and Human Sciences, Laboratory of Pharmacology, College of Nursing of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, SP, Brazil
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Catiane R. Silva;
Catiane R. Silva
‡Department of Psychiatric Nursing and Human Sciences, Laboratory of Pharmacology, College of Nursing of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, SP, Brazil
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Rhian M. Touyz;
Rhian M. Touyz
*Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa, Ontario, Canada
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Carlos R. Tirapelli
‡Department of Psychiatric Nursing and Human Sciences, Laboratory of Pharmacology, College of Nursing of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, SP, Brazil
Correspondence: Professor Carlos R. Tirapelli (email [email protected]).
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Publisher: Portland Press Ltd
Received:
July 06 2009
Revision Received:
November 12 2009
Accepted:
December 03 2009
Accepted Manuscript online:
December 03 2009
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2010 Biochemical Society
2010
Clin Sci (Lond) (2010) 118 (11): 657–668.
Article history
Received:
July 06 2009
Revision Received:
November 12 2009
Accepted:
December 03 2009
Accepted Manuscript online:
December 03 2009
Citation
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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