Circulation. 2001;104:700-704
doi: 10.1161/hc3201.092284
doi: 10.1161/hc3201.092284
(Circulation. 2001;104:700.)
© 2001 American Heart Association, Inc.
Basic Science Reports |
Increased Inducible Nitric Oxide Synthase Expression Contributes to Myocardial Dysfunction and Higher Mortality After Myocardial Infarction in Mice
From the Cardiology Research Laboratory, Departments of Medicine, Pharmacology, and Toxicology, and Departments of Physiology and Medicine (D.L.J.), University of Western Ontario, London, Ontario, Canada.
Correspondence to Dr Qingping Feng, Department of Medicine, London Health Sciences Centre, Victoria Campus, 375 South St, London, Ontario, Canada N6A 4G5. E-mail qfeng{at}uwo.ca
Background—— Inducible nitric oxide synthase (iNOS) is expressed in the myocardium after myocardial infarction (MI) and in heart failure. Its pathophysiological role in these conditions, however, is not clear. We hypothesized that increased NO production from iNOS expression causes myocardial dysfunction and results in higher mortality after MI.
Methods and Results—— MI was induced by left coronary artery ligation in iNOS-/- mutant and wild-type mice. Mortality was followed up for 30 days. MI resulted in a significant increase in mortality in both iNOS-/- and wild-type mice compared with sham operation (P<0.01). Mortality was significantly decreased and LV myocardial contractility was increased, however, in iNOS-/- mice compared with the wild-type mice (P<0.05). Five days after MI, myocardial iNOS mRNA expression, plasma nitrate and nitrite concentrations, and myocardial and plasma nitrotyrosine levels were significantly increased in wild-type compared with iNOS-/- mutant mice (P<0.05). Both basal LV +dP/dt and its response to dobutamine were significantly increased in iNOS-/- compared with the wild-type mice (P<0.05).
Conclusions—— Increased NO production from iNOS expression contributes to myocardial dysfunction and mortality after MI in mice.
Key Words: heart failure • nitric oxide • nitric oxide synthase • myocardial infarction
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