Deficiency of iNOS does not attenuate severe congestive heart failure in mice.
Inducible nitric oxide synthase (iNOS) has been implicated in the pathophysiology of congestive heart failure (CHF). Given the extensive evidence supporting this concept, we hypothesized that iNOS deficiency (iNOS(-/-)) would attenuate the severity of CHF in mice. Mice were subjected to permanent occlusion [myocardial infarction (MI)] of the proximal left anterior descending coronary artery to produce CHF. Cardiac function was assessed in vivo using echocardiography and ultraminiature ventricular pressure catheters. Sham wild-type (n = 17), sham iNOS(-/-) (n = 8), MI wild-type (n = 56), and MI iNOS(-/-) (n = 48) mice were subjected to MI (or sham MI) and followed for 1 mo. Deficiency of iNOS did not alter survival during CHF compared with wild type (35% vs. 32%, P = not significant). Furthermore, fractional shortening and cardiac output were not significantly different between wild-type (9.6 +/- 2.0% and 441 +/- 20 microl.min(-1).g(-1)) and iNOS(-/-) (9.8 +/- 1.3% and 471 +/- 26 microl.min(-1).g(-1)) mice. The extent of cardiac hypertrophy and pulmonary edema was also similar between wild-type and iNOS(-/-) mice. None of the indexes demonstrated any significant differences between iNOS(-/-) and wild-type mice subjected to MI. These findings indicate that deficiency of iNOS does not significantly affect severe CHF in mice after MI.
Jones
Steven P
SP
Division of Cardiology, Department of Medicine, University of Louisville School of Medicine, Kentucky, USA.
Greer
James J M
JJ
Ware
Paul D
PD
Yang
Jiang
J
Walsh
Kenneth
K
Lefer
David J
DJ
D000818:Animals; D004452:Echocardiography; D006321:Heart / Q000503:physiopathology; D006333:Heart Failure / Q000201:enzymology / Q000209:etiology / Q000503:physiopathology*; D006352:Heart Ventricles / Q000000981:diagnostic imaging; D006439:Hemodynamics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000150:complications / Q000000981:diagnostic imaging / Q000473:pathology; D019001:Nitric Oxide Synthase / Q000172:deficiency*; D052247:Nitric Oxide Synthase Type II; D012720:Severity of Illness Index; D016019:Survival Analysis; D016277:Ventricular Function, Left
D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse