Deficiency of iNOS does not attenuate severe congestive heart failure in mice

1 Division of Cardiology, Department of Medicine, University of Louisville School of Medicine, Louisville, Kentucky; and 2 Department of Molecular and Cellular Physiology, 3 Department of Surgery, and 4 Division of Cardiology, Department of Medicine, Louisiana State University Health Sciences Center, Shreveport, Louisiana; and 5 The Whitaker Cardiovascular Institute, Boston University Medical Center, Boston, Massachusetts Submitted 11 March 2004 ; accepted in final form 19 August 2004 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 µl·min –1 ·g –1 ) and iNOS –/– (9.8 ± 1.3% and 471 ± 26 µl·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. myocardial infarction; nitric oxide; physiology; inducible nitric oxide synthase Address for reprint requests and other correspondence: D. J. Lefer, Dept. of Molecular and Cellular Physiology, Louisiana State Univ. Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130 ( dlefer{at}lsuhsc.edu )