[Nitrates as thrombocyte function inhibitors].

Abstract

Besides their well-known relaxing effects on smooth muscle cells--the basis for vasodilation in peripheral arteries and veins and in epicardial coronary arteries--nitrates also exert effects on blood platelets. These occur by the same mechanisms operating in blood vessels, a penetration of the parent molecule or its active metabolites through the plasma membrane, the release of the reactive free radical NO, the stimulation of guanylate cyclase and the consequent increase of cytosolic levels of cyclic guanosinemonophosphate (cGMP). As a consequence, platelets become unspecifically less reactive to a variety of aggregating stimuli. When added to platelet suspensions nitrates indeed inhibit platelet aggregation by virtually all known stimuli. These in vitro anti-platelet effects require high concentrations of the drugs; however, recent evidence has been gathered that such inhibition of platelet function also occurs during the in vivo administration of nitrates. Such evidence derives from direct ex vivo studies with platelet aggregometry, from experiments showing synergism of nitrates with prostacyclin and the amplification of ex vivo effects with sulfhydryl group donors such as N-acetyl-cysteine, and, finally, from studies on the bleeding time. The effects of nitrates on blood platelets may be an explanation for the protection from death and reinfarction inferred on the basis of metaanalysis of several studies in acute myocardial infarction.