Ethanol induces vascular relaxation via redox-sensitive and nitric oxide-dependent pathways

Author(s)

Rocha, Juliana T. ^[1] ; Hipolito, Ulisses V. ^[2] ; Callera, Glaucia E. ^[3] ; Yogi, Alvaro ^[3] ; dos Anjos Neto Filho, Mario ^[4] ; Bendhack, Lusiane M. ^[4] ; Touyz, Rhian M. ^[3] ; Tirapelli, Carlos R. ^[1]

Affiliation

^[1] Univ Sao Paulo, Coll Nursing Ribeirao Preto, Pharmacol Lab, Dept Psychiat Nursing & Human Sci, BR-14040902 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Pharmacol, BR-14040902 Ribeirao Preto, SP - Brazil

^[3] Univ Ottawa, Ottawa Hosp Res Inst, Kidney Res Ctr, Ottawa, ON K1N 6N5 - Canada

^[4] Univ Sao Paulo, Fac Pharmaceut Sci, Pharmacol Lab, Dept Chem & Phys, BR-14040902 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: VASCULAR PHARMACOLOGY; v. 56, n. 1-2, p. 74-83, JAN-FEB 2012.
• Web of Science Citations: 9

Abstract

We investigated the role of reactive oxygen species (ROS) and nitric oxide (NO) in ethanol-induced relaxation. Vascular reactivity experiments showed that ethanol (0.03-200 mmol/L) induced relaxation in endothelium-intact and denuded rat aortic rings isolated from male Wistar rats. Pre-incubation of intact or denuded rings with L-NAME (non selective NOS inhibitor, 100 mu mol/L), 7-nitroindazole (selective nNOS inhibitor, 100 mu mol/L), ODQ (selective inhibitor of guanylyl cyclase enzyme, I mu mol/L), glibenclamide (selective blocker of ATP-sensitive K+ channels, 3 mu mol/L) and 4-aminopyridine (selective blocker of voltage-dependent K+ channels, 4-AP, 1 mmol/L) reduced ethanol-induced relaxation. Similarly, tiron (superoxide anion (O-2(-)) scavenger, 1 mmol/L) and catalase (hydrogen peroxide (H2O2) scavenger, 300 U/mL) reduced ethanol-induced relaxation to a similar extent in both endothelium-intact and denuded rings. Finally, prodifen (non-selective cytochrome P450 enzymes inhibitor, 10 mu mol/L) and 4-methylpyrazole (selective alcohol dehydrogenase inhibitor, 10 mu mol/L) reduced ethanol-induced relaxation. In cultured aortic vascular smooth muscle cells (VSMCs), ethanol stimulated generation of NO, which was significantly inhibited by L-NAME. In endothelial cells, flow cytometry studies showed that ethanol increased cytosolic Ca2+ concentration ({[}Ca2+]c), O-2(-) and cytosolic NO concentration ({[}NO]c). Tiron inhibited ethanol-induced increase in {[}Ca-2]c and {[}NO]c. The major new finding of this work is that ethanol induces relaxation via redox-sensitive and NO-cGMP-dependent pathways through direct effects on ROS production and NO signaling. These findings identify putative molecular mechanisms whereby ethanol, at pharmacological concentrations, influences vascular reactivity. (C) 2011 Elsevier Inc. All rights reserved. (AU)