Key result
Platelet nitric oxide resistance is an independent predictor of morbidity and mortality in unstable angina and can be partially reversed by agents like perindopril, perhexiline, and insulin.
Platelet resistance to nitric oxide is a distinct pathophysiological phenomenon in acute coronary syndromes and other cardiovascular conditions, which may impact the clinical efficacy of NO donors.
NO resistance may predict outcomes in unstable angina; hypothesis-generating for reversal, needs prospective validation before practice change.
Background Nitric oxide (NO) functions as a negative regulator of platelet aggregability, predominantly via activation of soluble guanylate cyclase (sGC); this is also relevant to the clinical efficacy of NO donors in management of acute coronary syndromes. However, we have discovered that acute coronary syndromes are associated with attenuation of platelet responsiveness to NO donors, independent of the phenomenon of nitrate tolerance. The phenomenon of platelet NO resistance has been documented to occur in association with a number of coronary risk factors (hypertension, diabetes, hyperlipidaemia) and also in nonischaemic forms of heart disease.
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Horowitz et al. (2009) conducted a review in Nitric oxide resistance in cardiovascular disease. Nitric oxide donors, sGC stimulators, and other agents was evaluated. Platelet nitric oxide resistance is an independent predictor of morbidity and mortality in unstable angina and can be partially reversed by agents like perindopril, perhexiline, and insulin.
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