Ventricular atrial natriuretic factor in the cardiomyopathic hamster model of congestive heart failure.

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.