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Type: Journal article
Title: Nitrate Resistance in platelets from patients with stable angina pectoris
Author: Chirkov, Y.
Holmes, A.
Chirkova, L.
Horowitz, J.
Citation: Circulation, 1999; 100(2):129-134
Publisher: Highwire Press
Issue Date: 1999
ISSN: 0009-7322
Abstract: <h4>Background</h4>Hemodynamic resistance to nitrates has been previously documented in congestive heart failure. In patients with stable angina pectoris (SAP), we have observed a similar phenomenon: decreased platelet response to disaggregating effects of nitroglycerin (NTG) and sodium nitroprusside (SNP).<h4>Methods and results</h4>In blood samples from normal subjects (n=32) and patients with SAP (n=56), we studied effects of NO donors (NTG and SNP) on ADP-induced platelet aggregation and on intraplatelet cGMP. NTG and SNP inhibited platelet aggregation in patients to lesser extents than in normal subjects (P<0.01). The cGMP-elevating efficacy of NTG and SNP was diminished in platelets from patients in comparison with those from normals (P<0.001). Inhibition of the anti-aggregatory effects of NTG and SNP by ODQ, a selective inhibitor of NO-stimulated guanylate cyclase, was significantly less pronounced in patients than in normal subjects. Content of O2- was higher in blood samples from patients than in those from normal subjects (P<0. 01). In blood samples from patients with SAP, but not in normal subjects, the O2- scavenger superoxide dismutase (combined with catalase) suppressed platelet aggregation (P<0.01) and increased the extent of anti-aggregatory effect of SNP (P<0.01).<h4>Conclusions</h4>In patients with SAP, platelets are less responsive to the anti-aggregating and cGMP-stimulating effects of NO donors; this may reflect both reduction in guanylate cyclase sensitivity to NO and inactivation of the released NO by O2-. The implied impairment of anti-platelet efficacy of endogenous NO (in the form of EDRF) may contribute to platelet hyperaggregability associated with angina pectoris.
Keywords: Blood Platelets
Angina Pectoris
Adenosine Diphosphate
Nitric Oxide Donors
Platelet Aggregation Inhibitors
Platelet Aggregation
Drug Resistance
Reference Values
Middle Aged
DOI: 10.1161/01.CIR.100.2.129
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