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Adelaide Research and Scholarship
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Schools and Disciplines
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School of Medicine
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Surgery
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Surgery (QEH) Publications
Permanent link to this item:
http://hdl.handle.net/2440/49009
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| Type: | Article |
| Title: | Platelet nitric oxide resistance: Pathogenesis and clinical implications |
| Author: | Chirkov, Yuliy
Horowitz, John D. |
| Citation: | Nitric Oxide-Biology and Chemistry, 2008; 19(Suppl 1):58-58 |
| Publisher: | Academic Press Inc Elsevier Science |
| Issue Date: | 2008 |
| ISSN: | 1089-8603 |
| School/Discipline: | Surgery |
Statement of
Responsibility: | Yuliy Y. Chirkov and John D. Horowitz |
| Abstract: | Platelet hyperaggregability and associated thrombosis have been documented in a number of cardiovascular diseases. Nitric oxide (NO), via activation of soluble guanylate cyclase, plays an important role in platelet physiology, providing a negative control over platelet aggregation. Endogenous NO is not only of the endothelial source, it is also released from activated platelets. Our extensive studies in patients with angina pectoris, chronic heart failure, diabetes and various cardiovascular risk factors have demonstrated that platelets from these subjects exhibit reduced responsiveness to the anti-aggregating efficacy of NO donors. We have termed this phenomenon “platelet NO resistance”. It results largely from a combination of “scavenging” of NO by superoxide anion radical and inactivation of platelet guanylate cyclase. NO resistance has been also documented in vasculature and is usually paralleled by endothelial dysfunction. In view of the physiological interactions between platelets and the endothelium, impaired responsiveness to NO can be viewed as a mediator of the pathological impact of oxidative stress on hemostasis, with resultant thrombosis in both coronary and peripheral arteries, and increased risk of ischemic events. Furthermore, NO resistance accounts for reduced pharmaco-activity of NO donors used in clinical practice, e.g., organic nitrates. Impaired NO responsiveness creates a potential problem, that ischemic patients, who are in greatest need of nitrate therapy, are least likely to respond. NO resistance may also be a prognostic tool; patients with impaired platelet responsiveness to NO have a significantly higher cardiovascular morbidity and mortality, compared to patients with preserved NO responsiveness. NO resistance is a potential target for pharmacological interventions. We have shown that a number of agents (ACE inhibitors, perhexiline, insulin and statins) ameliorate NO resistance and may exert their beneficial clinical effects partially by enhancing platelet and vascular NO responsiveness. Identification of patients with NO resistance might constitute a means for improved therapeutic decision-making. |
| RMID: | 0020084160 |
| DOI: | 10.1016/j.niox.2008.06.165 |
| Description (link): | http://www.elsevier.com/wps/find/journaldescription.cws_home/622926/description#description |
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| Appears in Collections: | Surgery (QEH) Publications
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