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Title: Cardioprotective activity of endogenous and exogenous nitric oxide on ischaemia reperfusion injury in isolated guinea pig hearts. Author: Masini E, Salvemini D, Ndisang JF, Gai P, Berni L, Moncini M, Bianchi S, Mannaioni PF. Journal: Inflamm Res; 1999 Nov; 48(11):561-8. PubMed ID: 10598011. Abstract: BACKGROUND: We evaluated the contribution of endogenous and exogenous nitric oxide (NO) in ischaemia reperfusion (IR) injury and histamine release in the isolated guinea pig heart. METHODS: Ischaemia reperfusion was performed in isolated Langendorff perfused guinea pig heart throughout the ligature of the left anterior descending coronary (LAD) artery for 20 min, and following the release of the ligature 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 nitrite (NO2-, one of the breakdown products of NO) released during IR was significantly lower than in the control hearts. These effects were accompanied 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 pathway, namely N(G)-monomethyl-L-arginine (L-NMMA, 10(-4) M) or nitroarginine methylester (L-NAME, 10(-5) M) significantly enhanced histamine and LDH release; 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-morpholinosydnonimine (SIN-1), glyceryl trinitrate (GTN), all at 10(-5) M, reduced histamine release, LDH release, calcium overload and MDA production induced by IR. These effects were amplified by concomitant perfusion with superoxide dismutase (SOD, 50 IU/ml). CONCLUSION: The endogenous production of NO provides significant myocardial protection from IR injury and histamine release. These effects were mimicked by various NO donors.[Abstract] [Full Text] [Related] [New Search]