title: Modulation of neutrophil activity by nitric oxide during acute myocardial ischaemia and reperfusion.
abstract: Nitric oxide (NO) exerts an inhibitory effect on polymorphonuclear neutrophil (PMN) function, via a cyclic GMP-mediated mechanism, while PMNs are known to play an important role in myocardial ischaemia-reperfusion injury (MI-R). Since the major source of NO, vascular endothelium, becomes functionally impaired during MI-R, it is attractive to hypothesize that it is this loss of endothelial nitric oxide production that allows PMN adherence and activation. The studies reviewed here add substance to this hypothesis. Authentic NO, administered during MI-R both reduces myocardial necrosis and PMN accumulation, while basal NO release, as estimated by coronary artery ring responses to L-NAME, an NO synthase inhibitor, declines during reperfusion with a time-course mirrored by PMN adherence in the same preparation. Reduction in infarct size and decreased PMN accumulation can also be demonstrated with L-arginine and NO donors. Since endothelial dysfunction leads to PMN adherence and PMNs have been shown to contribute to endothelial dysfunction, it seems probable that a positive feedback loop is generated during MI-R, leading to the amplification of PMN activity and subsequent myocardial damage.
authors.affiliation: Academic Cardiology Unit, St. Mary's Hospital Medical School, London, United Kingdom.
authors.forename: R M
authors.initials: RM
authors.lastname: Egdell
authors.forename: T
authors.initials: T
authors.lastname: Siminiak
authors.forename: D J
authors.initials: DJ
authors.lastname: Sheridan
mesh_terms: D000208:Acute Disease; D000818:Animals; D002448:Cell Adhesion; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D008213:Lymphocyte Activation; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000503:physiopathology; D009504:Neutrophils / Q000378:metabolism / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology*
chemical_list: D009569:Nitric Oxide