Impairment of platelet NO signalling in coronary artery spasm: role of hydrogen sulphide

Background and Purpose The pathophysiology of coronary artery spasm (CAS), with its associated ischaemic crises, is currently poorly understood treatment frequently ineffective. In view increasing evidence that platelet-based defects may occur in CAS patients, we investigated platelet reactivity patients whether symptomatic crises reflect activation platelet–endothelial interactions. Experimental Approach were evaluated during acute and/or chronic phases compared healthy control subjects. Inhibition ADP-induced aggregation by the NO donor sodium nitroprusside (SNP) plasma concentrations syndecan 1 (glycocalyx shedding marker), tryptase (mast cell marker) microparticles measured. Key Results SNP was diminished CAS, further (non-significant) deterioration whereas 1, increased. Treatment high-dose N-acetylcysteine (NAC) plus glyceryl trinitrate rapidly increased responsiveness to decreased concentrations. effect NAC on confirmed vitro mimicked H2S NaHS. Conversely, inhibition enzymatic production attenuated effect. Conclusion Implications substantial impairment signalling. During exacerbations, resistance aggravated, together mast damage both vasculature platelets. NAC, via release H2S, reverses terminates glycocalyx crises: This suggests donors correct pathophysiological anomalies underlying CAS.