过氧亚硝酸盐，即一氧化氮和超氧化物的产物，可导致离体灌注大鼠心脏的心肌损伤。

Peroxynitrite, the product of nitric oxide and superoxide, causes myocardial injury in the isolated perfused rat heart.

作者信息

Lopez B L, Liu G L, Christopher T A, Ma X L

机构信息

Division of Emergency Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA.

出版信息

Coron Artery Dis. 1997 Mar-Apr;8(3-4):149-53. doi: 10.1097/00019501-199703000-00005.

DOI:10.1097/00019501-199703000-00005

PMID:9237024

Abstract

BACKGROUND

Recent studies have determined that the product of NO and superoxide is peroxynitrite (ONOO-), an anion with deleterious tissue-oxidant effects.

OBJECTIVE

To examine the effects of ONOO- on the isolated perfused rat heart. Sprague-Dawley rat hearts were perfused with a cell-free, Krebs-Henseleit solution on a Langendorf perfusion apparatus. The hearts were subjected to 30 min infusions of vehicle (control); 10 mumol/l S-nitroso-N-acetylpenicillamine (SNAP), an NO donor; 10 mumol/l pyrogallol, a superoxide generator); 10 mumol/l SNAP plus 10 mumol/l pyrogallol, a mixture that generates peroxynitrite; or 10 mumol/l SNAP plus 10 mumol/l pyrogallol plus 300 U/ml superoxide dismutase.

RESULTS

SNAP or pyrogallol alone had no effect on cardiac function at the concentration used; however, infusion of the combination of SNAP and pyrogallol resulted in significant decreases in left ventricular developed pressure (to 83 +/- 4%, P < 0.01, versus vehicle) and dp/dtmax (to 76 +/- 6.2%, P < 0.01, versus vehicle), and also resulted in a significant increase in production of lactic dehydrogenase (to 118 +/- 4%, P < 0.01, versus vehicle). The administration of superoxide dismutase with SNAP and pyrogallol reversed these deleterious effects.

CONCLUSION

These results suggest that the formation of peroxynitrite significantly enhances the toxicities of .NO and O2.- and causes marked cardiac injury.

摘要

背景

最近的研究已确定，一氧化氮（NO）和超氧化物的产物是过氧亚硝酸盐（ONOO-），一种具有有害组织氧化作用的阴离子。

目的

研究过氧亚硝酸盐对离体灌注大鼠心脏的影响。采用Langendorff灌注装置，用无细胞的Krebs-Henseleit溶液灌注Sprague-Dawley大鼠心脏。对心脏进行30分钟的灌注，灌注液分别为：溶剂（对照）；10 μmol/L的S-亚硝基-N-乙酰青霉胺（SNAP，一种NO供体）；10 μmol/L的邻苯三酚（一种超氧化物生成剂）；10 μmol/L的SNAP加10 μmol/L的邻苯三酚（一种生成过氧亚硝酸盐的混合物）；或10 μmol/L的SNAP加10 μmol/L的邻苯三酚加300 U/ml超氧化物歧化酶。

结果

单独使用SNAP或邻苯三酚在所使用的浓度下对心脏功能无影响；然而，灌注SNAP和邻苯三酚的组合导致左心室舒张末压显著降低（降至83±4%，与溶剂组相比，P<0.01）和dp/dtmax显著降低（降至76±6.2%，与溶剂组相比，P<0.01），并且还导致乳酸脱氢酶的生成显著增加（增至118±4%，与溶剂组相比，P<0.01）。超氧化物歧化酶与SNAP和邻苯三酚联合使用可逆转这些有害作用。