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 (iNO[S.sup.-/-]) 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 iNO[S.sup.-/-] (n = 8), MI wild-type (n = 56), and MI iNO[S.sup.-/-] (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 [+ or -] 2.0% and 441 [+ or -] 20 [micro]l x [min.sup.-1] x [g.sup.-1]) and iNO[S.sup.-/-](9.8 [+ or -] 1.3% and 471 [+ or -] 26 [micro]l x [min.sup.-1] x [g.sup.-1]) mice. The extent of cardiac hypertrophy and pulmonary edema was also similar between wild-type and iNO[S.sup.-/-] mice. None of the indexes demonstrated any significant differences between iNO[S.sup.-/-] 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