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The opposite effects of nitric oxide donor, S‐nitrosoglutathione, on myocardial ischaemia/reperfusion injury in diabetic and non‐diabetic mice
Author(s) -
Liu Yi,
Xia Chenhai,
Wang Rutao,
Zhang Jinglong,
Yin Tao,
Ma Yanzuo,
Tao Ling
Publication year - 2017
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12781
Subject(s) - peroxynitrite , nitric oxide , diabetes mellitus , s nitrosoglutathione , reperfusion injury , streptozotocin , oxidative stress , pharmacology , ischemia , superoxide dismutase , superoxide , medicine , intraperitoneal injection , enos , nitrotyrosine , nitric oxide synthase , apocynin , chemistry , nadph oxidase , endocrinology , biochemistry , glutathione , enzyme
Summary Nitric oxide is a potent anti‐apoptotic and cardioprotective molecule in healthy animals. However, recent study demonstrates that overexpression of eNOS exacerbates the liver injury in diabetic animals. whether diabetes may also alter NO 's biologic activity in ischaemic/reperfused heart remains unknown. The present experiment was designed to determine whether the nitric oxide donor, S‐nitrosoglutathione, may exert different effects on diabetic and non‐diabetic myocardial ischaemia/reperfusion ( MI /R) injury. Diabetic state was induced in mice by multiple intraperitoneal injections of low‐dose streptozotocin ( STZ ). The control or diabetic mice were subjected to 30 minutes ischaemia and 3 or 24 hours reperfusion. At 10 minutes before reperfusion, diabetic and non‐diabetic mice were received an intraperitoneal injection of S‐nitrosoglutathione ( GSNO , a nitric oxide donor, 1 μmol/kg). GSNO attenuated MI /R injury in non‐diabetic mice, as measured by improved cardiac function, reduced infarct size and decreased cardiomyocyte apoptosis. In contrast, GSNO failed to attenuate but, rather, aggravated the MI /R injury in diabetic mice. Mechanically, the diabetic heart exhibited an increased nitrative/oxidative stress level, as measured by peroxynitrite formation, compared with non‐diabetic mice. Co‐administration of GSNO with EUK 134 (a peroxynitrite scavenger) or Mn TE ‐2‐PyP5 (a superoxide dismutase mimetic) or Apocynin (a NADPH oxidase inhibitor) 10 minutes before reperfusion significantly decreased the MI /R‐induced peroxynitrite formation and the MI /R injury. Collectively, the present study for the first time demonstrated that diabetes may cause superoxide overproduction, increase NO inactivation and peroxynitrite formation, and thus convert GSNO from a cardioprotective molecule to a cardiotoxic molecule.