Nitric oxide resistance at the platelet level: pathophysiology and therapeutic implications

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.