Decrease in Endogenous Cgrp Release in Nitroglycerin Tolerance: Role of Aldh-2.
From: Department of Pharmacology, School of Pharmaceautical Sciences, Central South University, Changsha 410078, China.
European journal of pharmacology
- Publish Date: Sep 2007
- ISSN: 0014-2999
- Volume: 571
- Issue: 1
- Pages: 44-50
- Medium: Print
- Language: English
- Citation (JAMA): Chen Yue-Rong, Nie Sheng-Dan, Shan Wang, et al. Decrease in Endogenous Cgrp Release in Nitroglycerin Tolerance: Role of Aldh-2.. Eur. J. Pharmacol. Sep 2007;571:44-50
Abstract
In the present study, we tested whether the decreased release of calcitonin gene-related peptide (CGRP) observed in nitroglycerin tolerance is associated with the decrease in aldehyde dehydrogenase (ALDH-2) activity. We further investigated the possible involvement of reactive oxygen species in the decrease in ALDH-2 activity. Tolerance was induced by exposure of isolated rat thoracic aortas and human umbical vein endothelial cells (HUVEC) to nitroglycerin in vitro or by pretreatment with nitroglycerin for 8 days in vivo. Pretreatment with ALDH-2 inhibitors and nitroglycerin significantly attenuated vasodilator responses to nitroglycerin concomitantly with a decrease in the release of CGRP from the isolated thoracic aorta. Nitroglycerin produced a depressor effect concomitantly with an increase in plasma concentrations of CGRP, and the effect of nitroglycerin was attenuated after pretreatment with an inhibitor of ALDH-2 or nitroglycerin for 8 days. Exposure of HUVEC to nitroglycerin for 16 h increased reactive oxygen species production and decreased ALDH-2 activity as well as cGMP production in a time-and concentration-dependent manner. Pretreatment with an ALDH-2 inhibitor also significantly decreased the cGMP production. However, tolerance to nitroglycerin in HUVEC was restored in the presence of N-acetylcysteine or captopril. The present results suggest that nitrate tolerance is, at least partially, associated with a decrease in endogenous CGRP release via a decrease in ALDH-2 activity as a result of stimulation of reactive oxygen species production.
Mesh Headings (Keywords): Acetylcysteine, Aldehyde Dehydrogenase, Angiotensin-Converting Enzyme Inhibitors, Animals, Aorta, Thoracic, Blood Pressure, Calcitonin Gene-Related Peptide, Captopril, Cell Line, Chloral Hydrate, Cyanamide, Cyclic GMP, Dose-Response Relationship, Drug, Drug Interactions, Drug Tolerance, Endothelial Cells, Humans, Male, Nitric Oxide Donors, Nitroglycerin, Rats, Rats, Wistar, Reactive Oxygen Species, Vasodilation
Check for Full Text / PubMed Unique Identifier (PMID): 17585900
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