Nitrate Resistance In Platelets From Patients With Stable Angina Pectoris

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Abstract
Background —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). Methods and Results —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 P 2 − was higher in blood samples from patients than in those from normal subjects ( P 2 − scavenger superoxide dismutase (combined with catalase) suppressed platelet aggregation ( P P Conclusions —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 O 2 − . The implied impairment of anti-platelet efficacy of endogenous NO (in the form of EDRF) may contribute to platelet hyperaggregability associated with angina pectoris.