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

Rocha, J.T., Hipolito, U.V., Callera, G.E., Yogi, A., Filho, A., Bendhack, L.M., Touyz, R.M. and Tirapelli, C.R. (2012) Ethanol induces vascular relaxation via redox-sensitive and nitric oxide-dependent pathways. Vascular Pharmacology, 56(1-2), pp. 74-83. (doi: 10.1016/j.vph.2011.11.006)

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 μmol/L), 7-nitroindazole (selective nNOS inhibitor, 100 μmol/L), ODQ (selective inhibitor of guanylyl cyclase enzyme, 1 μmol/L), glibenclamide (selective blocker of ATP-sensitive K+ channels, 3 μmol/L) and 4-aminopyridine (selective blocker of voltage-dependent K+ channels, 4-AP, 1 mmol/L) reduced ethanol-induced relaxation. Similarly, tiron (superoxide anion (O2−) 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 μmol/L) and 4-methylpyrazole (selective alcohol dehydrogenase inhibitor, 10 μmol/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), O2- and cytosolic NO concentration ([NO]c). Tiron inhibited ethanol-induced increase in [Ca2 +]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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Touyz, Professor Rhian
• Authors: Rocha, J.T., Hipolito, U.V., Callera, G.E., Yogi, A., Filho, A., Bendhack, L.M., Touyz, R.M., and Tirapelli, C.R.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Vascular Pharmacology
• ISSN: 1537-1891
• ISSN (Online): 1879-3649
• Published Online: 06 December 2011