The nitric oxide redox sibling nitroxyl partially circumvents impairment of platelet nitric oxide responsiveness

Abstract

Impaired platelet responsiveness to nitric oxide (NO resistance) is a common characteristic of many cardiovascular disease states and represents an independent risk factor for cardiac events and mortality. NO resistance reflects both scavenging of NO by superoxide (O2-), and impairment of the NO receptor, soluble guanylate cyclase (sGC). There is thus an urgent need for circumvention of NO resistance in order to improve clinical outcomes. Nitroxyl (HNO), like NO, produces vasodilator and anti-aggregatory effects, largely via sGC activation, but is not inactivated by O2-. We tested the hypothesis that HNO circumvents NO resistance in human platelets. In 57 subjects with or without ischemic he..