Rm. Egdell et al., MODULATION OF NEUTROPHIL ACTIVITY BY NITRIC-OXIDE DURING ACUTE MYOCARDIAL-ISCHEMIA AND REPERFUSION, Basic research in cardiology, 89(6), 1994, pp. 499-509
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.