To study the role of atrial natriuretic peptide (ANP) in chronic heart failure, ANP synthesis, storage, and release were examined by measuring atrial ANP messenger ribonucleic acid (mRNA) levels and atrial and plasma ANP concentrations in rats with myocardial infarction produced by coronary artery ligation. Three groups were defined as the following: 1) controls, sham-operated, or operated, but noninfarcted; 2) moderate infarcts, involving 5-30% of the left ventricular circumference; and 3) large infarcts (greater than or equal to 30%). In addition, to determine a possible modulation by dietary Na intake on ANP levels in heart failure, plasma immunoreactive ANP (iANP) levels were measured in rats with and without infarcts given low, regular, or high Na intake for 2 wk, by which time all groups were in neutral balance. Plasma iANP levels varied directly with increasing infarct and atrial sizes, irrespective of Na intake. In contrast, atrial ANP concentration varied inversely with increasing infarct size. The ANP mRNA content index, a measure of total atrial ANP mRNA, was significantly increased in rats with large infarcts compared with control rats. These results indicate that in rats with myocardial infarction, the severity of left ventricular dysfunction, as inferred from infarct size, but not chronic Na intake, is the primary determinant of the extent of activation of the ANP system. Elevated circulating ANP levels are maintained through enhanced atrial synthesis and release. ANP may thus play an important role in the hemodynamic and renal adaptations to chronic heart failure.
A functional role for endogenous atrial natriuretic peptide in a canine model of early left ventricular dysfunction.
