Cardioprotective activity of endogenous and exogenous nitric oxide on ischaemia reperfusion injury in isolated guinea pig hearts

Background: We evaluated the contribution of endogenous and exogenous nitri c oxide (NO) in ischaemia reperfusion (IR) injury and histamine release in the isolated guinea pig heart. Methods. Ischaemia reperfusion was performed in isolated Langendorff perfus ed guinea pig heart throughout the ligature of the left anterior descending coronary (LAD) artery for 20 min, and following the release of the ligatur e for a further 20 min. Results: IR promoted a linear release of lactate dehydrogenase (LDH) and a preferential release of histamine in the reperfusion phase. The amount of n itrite (NO2- one of the breakdown products of NO) released during IR was si gnificantly lower than in the control hearts. These effects were accompanie d by an increase in calcium levels and malonyl-dialdehyde (MDA) production in the left ventricle and by a decrease in cardiac mast cell metachromasia. Perfusion of the hearts with two inhibitors of the nitric oxide synthase p athway, namely N-G-monomethyl-L-arginine (L-NMMA, 10(-4) M) or nitroarginin e methylester (L-NAME, 10(-5) M) significantly enhanced histamine and LDH r elease; these effects were attenuated by co-infusion with L-arginine (10(-4 ) M) but not D-arginine (10(-4) M), while L-arginine ( 10(-4) M) alone had no effect. Perfusion of the heart with sodium nitroprusside (SNP), 3-morpho linosydnonimine (SIN-1), glyceryl trinitrate (GTN), all at 10(-5) M, reduce d histamine release, LDH release, calcium overload and MDA production induc ed by IR. These effects were amplified by concomitant perfusion with supero xide dismutase (SOD, 50 IU/ml). Conclusion: The endogenous production of NO provides significant myocardial protection from IR injury and histamine release. These effects were mimick ed by various NO donors.