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https://hdl.handle.net/2440/41970
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Type: | Journal article |
Title: | Impaired tissue responsiveness to organic nitrates and nitric oxide: A new therapeutic frontier? |
Author: | Chirkov, Y. |
Citation: | Pharmacology and Therapeutics, 2007; 116(2):287-305 |
Publisher: | Pergamon-Elsevier Science Ltd |
Issue Date: | 2007 |
ISSN: | 0163-7258 1879-016X |
Editor: | Horowitz, J. |
Statement of Responsibility: | Yuliy Y. Chirkova and John D. Horowitz |
Abstract: | Nitric oxide (NO) is a physiologically important modulator of both vasomotor tone and platelet aggregability. These effects of NO are predominantly mediated by cyclic guanosine-3,'5'-monophosphate (cGMP) via activation of soluble guanylate cyclase. However, in patients with ischemic heart disease, platelets and coronary/peripheral arteries are hyporesponsive to the antiaggregatory and vasodilator effects of NO donors. NO resistance is also associated with a number of coronary risk factors and presents in different disease states. It correlates with conventional measures of "endothelial dysfunction," and represents a multifaceted disorder, in which smooth muscle and platelet NO resistance are equally important, as sites of abnormal NO-driven physiology. NO resistance results largely from a combination of "scavenging" of NO by superoxide anion radical (O(2)(-)) and of (reversible) inactivation of soluble guanylate cyclase. It constitutes an impaired physiological response to endogenous NO (endothelium-derived relaxing factor, EDRF) and, as such, may contribute to the increased risk of ischemic events. Impairment in responsiveness to NO in ischemic patients implies a potential problem that those patients, in greatest need of nitrate therapy, may be least likely to respond. The prognostic impact of NO resistance at vascular and platelet levels has been demonstrated in patients with ischemic heart disease, and it has been shown that a number of agents (angiotensin-converting enzyme [ACE] inhibitors, perhexiline, insulin, and possibly statins) ameliorate this anomaly. The current review examines different aspects of the "NO resistance" phenomenon and discusses some related methodological issues. |
Keywords: | Vasodilatation Organic nitrates Nitric oxide Cardiovascular disease Vascular endothelium |
Description: | Copyright © 2007 Published by Elsevier Inc. |
DOI: | 10.1016/j.pharmthera.2007.06.012 |
Description (link): | http://www.elsevier.com/wps/find/journaldescription.cws_home/525486/description#description |
Published version: | http://dx.doi.org/10.1016/j.pharmthera.2007.06.012 |
Appears in Collections: | Aurora harvest 6 Medicine publications |
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