MODULATION OF NEUTROPHIL ACTIVITY BY NITRIC-OXIDE DURING ACUTE MYOCARDIAL-ISCHEMIA AND REPERFUSION

Nitric oxide (NO) exerts an inhibitory effect on polymorphonuclear neu trophil (PMN) function, via a cyclic GMP-mediated mechanism, while PMN s are known to play an important role in myocardial ischaemia-reperfus ion injury (MI-R). Since the major source of NO, vascular endothelium, becomes functionally impaired during MI-R, it is attractive to hypoth esize that it is this loss of endothelial nitric oxide production that allows PMN adherence and activation. The studies reviewed here add su bstance to this hypothesis. Authentic NO, administered during MI-R bot h reduces myocardial necrosis and PMN accumulation, while basal NO rel ease, as estimated by coronary artery ring responses to L-NAME, an NO synthase inhibitor, declines during reperfusion with a time-course mir rored by PMN adherence in the same preparation. Reduction in infarct s ize and decreased PMN accumulation can also be demonstrated with L-arg inine and NO donors. Since endothelial dysfunction leads to PMN adhere nce and PMNs have been shown to contribute to endothelial dysfunction, it seems probable that a positive feedback loop is generated during M I-R, leading to the amplification of PMN activity and subsequent myoca rdial damage.