Cardioprotective activity of endogenous and exogenous nitric oxide on ischaemia reperfusion injury in isolated guinea pig hearts
Cardioprotective activity of endogenous and exogenous nitric oxide on ischaemia reperfusion injury in isolated guinea pig hearts
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内源性和外源性一氧化氮对离体豚鼠心脏缺血再灌注损伤的心脏保护作用
作者：
E. Masini;Daniela Salvemini;J. Ndisang;P. Gai;L. Berni;M. Moncini;S. Bianchi;P. Mannaioni
Abstract.Background:本实验观察了内源性和外源性一氧化氮（NO）在离体豚鼠心脏缺血再灌注（IR）损伤和组胺释放中的作用。方法：结扎豚鼠冠状动脉左前降支（LAD）20 min后，再结扎20 min，进行Langendorff离体心脏缺血再灌注。结果：IR促进再灌注期乳酸脱氢酶（LDH）的线性释放和组胺的优先释放。IR期间释放的亚硝酸盐（NO 2-，NO的分解产物之一）的量显著低于对照组心脏。这些作用伴随着左心室钙水平和丙二醛（MDA）生成的增加以及心脏肥大细胞异染性的减少。用两种一氧化氮合酶途径抑制剂，即NG-单甲基-L-精氨酸灌注心脏（L-NMMA，10-4 M）或硝基精氨酸甲酯（L-NAME，10 ~（-5）M）显著促进组胺和LDH释放;通过与L-精氨酸（10-4 M）共输注而不是与D-精氨酸（10-4 M）共输注，这些作用减弱，而单独的L-精氨酸（10-4 M）没有作用。用硝普钠（SNP）、3-吗啉基丙酮亚胺（SIN-1）、三硝酸甘油（GTN）灌流心脏，浓度均为10 ~（-5）M，可减少IR引起的组胺释放、LDH释放、钙超载和MDA生成，同时灌流超氧化物歧化酶（SOD，50 IU/ml）可增强上述作用。结论：内源性NO对缺血再灌注损伤和组胺释放具有保护作用。这些效果被各种NO供体模仿。
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 malonyldialdehyde (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 NG-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.
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影响因子：
37.8
作者：
Yi-wu Xie;M. Wolin
通讯作者：
Yi-wu Xie;M. Wolin
DOI：
10.1073/pnas.87.4.1620
发表时间：
1990-02-01
影响因子：
11.1
作者：
BECKMAN, JS;BECKMAN, TW;FREEMAN, BA
通讯作者：
FREEMAN, BA
DOI：
10.1152/ajpheart.1997.272.5.h2327
发表时间：
1997-05-01
影响因子：
4.8
作者：
Liu, PT;Hock, CE;Wong, PYK
通讯作者：
Wong, PYK
再灌注期间冠状动脉内 L-精氨酸可改善内皮功能并减少梗塞面积。
DOI：
10.1152/ajpheart.1992.263.6.h1650
发表时间：
1992
期刊：
The American journal of physiology
影响因子：
--
作者：
Nakanishi,K;Vinten-Johansen,J;Lefer,DJ;Zhao,Z;Fowler3rd,WC;McGee,DS;Johnston,WE
通讯作者：
Johnston,WE