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Type: Journal article
Title: Suppressed anti-aggregating and cGMP-elevating effects of sodium nitroprusside in platelets from patients with stable angina pectoris
Author: Chirkov, Y.
Chirkova, L.
Horowitz, J.
Citation: Naunyn-Schmiedebergs Archives of Pharmacology, 1996; 354(4):520-525
Publisher: Springer-Verlag
Issue Date: 1996
ISSN: 0028-1298
Statement of
Yuliy Y. Chirkov, Larissa P. Chirkova, John D. Horowitz
Abstract: Platelet hyperactivity plays an important role in the pathogenesis of cardio-vascular diseases. In patients with stable angina pectoris, we have recently demonstrated that nitroglycerin suppressed the increased platelet aggregability. The anti-aggregating effect of NTG and other nitrovasodilators is mediated by platelet guanylate cyclase, which generates cyclic GMP (cGMP) in response to nitric oxide (NO) liberated from the nitrovasodilator molecule. In the current study we utilised a more “direct” NO donor, sodium nitroprusside (SNP), to examine reversal of ADP-induced platelet aggregation in comparison with intraplatelet cGMP elevation in platelets from normal subjects (n = 22) and patients with stable angina pectoris (n = 23). Concentrations of SNP associated with 50% reversal of aggregation were 2.7 ± 0.4 × 10−7 mol/L with normal subjects and 4.5 ± 0.5 × 10−6 mol/L with patients (P < 0.01). SNP produced a concentration-dependent elevation of intraplatelet cGMP content: with 10−4 mol/L SNP this was 17-fold for normals and 5-fold for patients (P < 0.01). An increase in cAMP content was seen only with 10−4 mol/L SNP, and was 157 ± 11% of baseline in platelets from normal subjects and 138 ± 14% in patients. There was a strong interrelationship between cGMP-stimulating and anti-aggregating effects of SNP. The decrease in cGMP responsiveness to SNP was not related to a dysfunction of platelet guanylate cyclase; neither basal nor SNP-stimulated activity of the enzyme varied significantly between normal subjects and patients. Lipophilic derivatives of cGMP (db-cGMP) and cAMP (db-cAMP) caused reversal of aggregation; there was a nonsignificant trend towards decreased responsiveness of platelets from patients to both db-cGMP and db-cAMP. The observed decrease in responsiveness of platelets from angina patients to anti-aggregating effects of the exogenous NO donor, SNP, can therefore be attributed to suppressed cGMP accumulation. These results imply reduced platelet sensitivity to endogenous NO (endothelium-derived relaxing factor); this might contribute to platelet hyperaggregability observed in angina pectoris.
Keywords: Platelet aggregation; Stable angin pectoris; Sodium nitroprusside; cGMP; Guanylate cyclase
Rights: © Springer-Verlag 1996
DOI: 10.1007/BF00168445
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