ATRIAL-NATRIURETIC-PEPTIDE FRAGMENTS IN DOGS WITH EXPERIMENTAL HEART-FAILURE

1. This study in the canine arteriovenous (AV) fistula model of high-o utput heart failure (HOHF) evaluated the chronic temporal changes in p lasma ANF and pro ANF 31-67 and their relationship to body-fluid balan ce and the renin-aldosterone axis. In addition, the haemodynamic, horm onal and renal excretory effects of synthetic pro ANF 31-67 infusions were examined in normal and AV fistula dogs with compensated HOHF. 2. Following the construction of the AV fistula, the dogs exhibited chron ic parallel elevations in right atrial pressure and the plasma concent rations of ANF and pro ANF 31-67. The gradual increases in the two pep tides were associated with a gradual decrease in plasma renin activity and the re-establishment of sodium balance. 3. In normal and compensa ted AV fistula dogs, synthetic pro ANF 31-67 produced similar signific ant reductions in arterial blood pressure, right atrial pressure and e levations in urinary sodium excretion. These effects were not associat ed with increases in plasma or urinary cyclic GMP (cGMP). 4. These res ults suggest that the elevation in the endogenous circulating levels o f pro ANF 31-67 in the AV fistula dogs may represent one chronic adapt ive mechanism to achieve body fluid homeostasis. Furthermore, via pote ntially different mechanisms of action, ANF and pro ANF 31-67 may coor dinate and contribute to the regulation of haemodynamic and renal func tion during physiological and pathophysiological situations.