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Ventricular atrial natriuretic factor in the cardiomyopathic hamster model of congestive heart failure
H A Franch1, R A Dixon, E H Blaine
1Department of Pharmacology, Merck Sharp & Dohme Research Laboratories, West Point, PA 19486.
Insights
In heart failure, the heart ventricle, not just the atria, significantly increases production and storage of atrial natriuretic factor (ANF). This suggests ventricles become a key ANF source during congestive heart failure.
Area of Science:
- Cardiology
- Molecular Biology
- Physiology
Background:
- Cardiac atria are considered the primary source of atrial natriuretic factor (ANF).
- It remains unknown if other cardiac regions contribute to ANF production during disease states with elevated ANF levels.
Purpose of the Study:
- To investigate the contribution of ventricular tissue to total cardiac ANF production and storage in a cardiomyopathic hamster model of congestive heart failure.
Main Methods:
- Measured immunoreactive ANF in plasma, atrial, and ventricular extracts.
- Quantified ANF mRNA levels in atrial and ventricular tissues.
- Compared findings between normal and cardiomyopathic hamsters at varying stages of heart failure.
Main Results:
- Cardiomyopathic hamsters exhibited higher plasma ANF levels.
- Atrial ANF concentration decreased significantly with increasing heart failure severity.
- Ventricular ANF concentration and mRNA levels increased substantially in moderate to severe heart failure, accounting for up to 23% of total cardiac ANF stores.
Conclusions:
- Ventricular ANF production and storage increase significantly in congestive heart failure.
- The ventricle emerges as a crucial source of ANF in heart failure, compensating for atrial deficits.
Abstract:
Cardiac atria are thought to be the principle source of plasma atrial natriuretic factor (ANF), a potent natriuretic and diuretic peptide. Whether other ANF production sites are recruited in disease states exhibiting elevated plasma ANF levels is not known. Accordingly, in the cardiomyopathic hamster, an animal model of congestive heart failure with high circulating levels of ANF, contribution of ventricular tissue to total cardiac ANF production and storage was investigated. Measurements were made of immunoreactive ANF in plasma and in atrial and ventricular extracts as well as ANF mRNA levels in the atria and ventricles from normal and cardiomyopathic golden Syrian hamsters. Plasma ANF levels were higher in cardiomyopathic than in control animals. The atrial concentration of ANF (per milligram atrial weight) was 50% and 83% lower in moderate and severe congestive heart failure, respectively, when compared with controls, while atrial ANF mRNA content of cardiomyopathic hamsters was not significantly different from normal hamsters. The ventricular concentration of ANF was 3 times and 7 times higher in animals in moderate and severe heart failure when compared with controls. In severe heart failure, ventricular ANF accounted for 23% of total cardiac stores of ANF. Ventricular ANF mRNA levels were 7 times and 13 times higher in hamsters in moderate and severe heart failure as compared with control animals. Therefore, significant increases in both ANF content and ANF mRNA in ventricles of hamsters in moderate to severe heart failure suggest that the ventricle could be an important source of ANF in congestive heart failure.