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Increased inducible nitric oxide synthase in skeletal muscle biopsies from patients with chronic heart failure
V Adams1, J Yu, S Möbius-Winkler
1Heart-Center, University of Leipzig, Germany.
Abstract:
In addition to left ventricular pump failure and low cardiac output, structural and metabolic alterations of skeletal muscle are thought to contribute to exercise intolerance seen in patients with CHF. Studies using cardiac myocytes have implicated nitric oxide elaborated by inducible nitric oxide synthase (iNOS) as a potential agent associated with the genesis of dilated cardiomyopathy. The present study was designed to locate iNOS in the working skeletal muscle of patients with congestive heart failure. Specific antibodies were used to detect iNOS by immunohistochemistry in skeletal muscle biopsies (m. vastus lateralis) of 37 patients with left ventricular pump failure and 8 normal controls. The expression was restricted to skeletal muscle myocytes and was increased five- to ninefold in patients with chronic heart failure. There was no statistically significant difference in iNOS expression between patients with dilated cardiomyopathy and those with ischemic cardiomyopathy. The finding of a locally increased expression of iNOS and the experimental evidence that NO attenuates the contractile performance of the skeletal muscle suggest that the expression of iNOS may be responsible for the exercise intolerance seen in patients with chronic heart failure.
Insights
Skeletal muscle in chronic heart failure patients shows increased inducible nitric oxide synthase (iNOS). This enzyme
Area of Science:
- Cardiology
- Skeletal Muscle Physiology
- Molecular Biology
Background:
- Exercise intolerance in chronic heart failure (CHF) is linked to skeletal muscle changes.
- Nitric oxide synthase (NOS) and its role in cardiac function are under investigation.
Purpose of the Study:
- To investigate the presence and expression of inducible nitric oxide synthase (iNOS) in the skeletal muscle of CHF patients.
- To explore the potential link between iNOS expression and exercise intolerance in CHF.
Main Methods:
- Immunohistochemistry was used to detect iNOS expression.
- Skeletal muscle biopsies (m. vastus lateralis) were obtained from 37 CHF patients and 8 healthy controls.
- Specific antibodies were employed to quantify iNOS in skeletal muscle myocytes.
Main Results:
- iNOS expression was significantly increased (five- to ninefold) in the skeletal muscle of CHF patients compared to controls.
- iNOS expression was localized to skeletal muscle myocytes.
- No significant difference in iNOS expression was observed between dilated and ischemic cardiomyopathy subtypes.
Conclusions:
- Increased iNOS expression in skeletal muscle is a feature of chronic heart failure.
- The findings suggest that elevated iNOS in skeletal muscle may contribute to exercise intolerance in CHF patients.
- Nitric oxide (NO) produced by iNOS may impair skeletal muscle contractile function.