Increased inducible nitric oxide synthase expression contributes to myocardial dysfunction and higher mortality after myocardial infarction in mice.
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.


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.
Feng
Q
Q
Cardiology Research Laboratory, Department of Medicine, University of Western Ontario, London, Ontario, Canada. qfeng@uwo.ca
Lu
X
X
Jones
D L
DL
Shen
J
J
Arnold
J M
JM
D000818:Animals; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D005838:Genotype; D006352:Heart Ventricles / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D006439:Hemodynamics / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009200:Myocardial Contraction / Q000502:physiology; D009203:Myocardial Infarction / Q000201:enzymology* / Q000401:mortality / Q000503:physiopathology; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000097:blood; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015996:Survival Rate; D013997:Time Factors; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
D009566:Nitrates; D009573:Nitrites; D012333:RNA, Messenger; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse