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Deficiency of iNOS does not attenuate severe congestive heart failure in mice
Steven P Jones1, James J M Greer, Paul D Ware
1Division of Cardiology, Department of Medicine, University of Louisville School of Medicine, Kentucky, USA.
Abstract:
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.
Insights
Inducible nitric oxide synthase (iNOS) deficiency did not impact the severity of congestive heart failure (CHF) in mice following myocardial infarction. These findings suggest iNOS is not a significant therapeutic target for severe CHF in this model.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Pathophysiology
Background:
- Inducible nitric oxide synthase (iNOS) plays a role in the development of congestive heart failure (CHF).
- Previous research suggests iNOS contributes to CHF pathophysiology.
Purpose of the Study:
- To investigate the hypothesis that iNOS deficiency attenuates CHF severity in a mouse model.
- To determine the impact of iNOS absence on cardiac function and survival post-myocardial infarction (MI).
Main Methods:
- Myocardial infarction (MI) was induced in wild-type and iNOS-deficient mice via coronary artery ligation.
- Cardiac function was assessed using echocardiography and ventricular pressure catheters.
- Survival, cardiac hypertrophy, and pulmonary edema were evaluated over one month.
Main Results:
- iNOS deficiency did not significantly alter survival rates in mice with CHF compared to wild-type controls.
- Fractional shortening and cardiac output were comparable between wild-type and iNOS-deficient groups.
- The extent of cardiac hypertrophy and pulmonary edema showed no significant differences between groups.
Conclusions:
- Deficiency of inducible nitric oxide synthase (iNOS) does not significantly affect the severity of congestive heart failure (CHF) in mice after myocardial infarction (MI).
- These results indicate that iNOS may not be a critical factor in the progression of severe CHF in this experimental model.
