THE ROLE OF ATRIAL-NATRIURETIC-FACTOR [ALPHA-HUMAN ANF(99-126)] IN THE HORMONAL AND RENAL ADAPTATION TO SODIUM DEFICIENCY

Atrial natriuretic factor (ANF) inhibits renin and aldosterone secreti on and enhances natriuresis in short term experiments. For studying th e role of ANF in the chronic hormonal and renal adaptation to sodium r estriction, we infused alpha-human ANF iv at a low dose (0.15-0.2 mu g /min) for 6 days into five normal male volunteers on a low sodium diet (LS; 15 mmol Na+/day) to mimic ANF levels observed in a preceding hig h sodium period (HS; 250 mmol/day). Endocrine (ANF, PRA, and aldostero ne) and renal parameters (urine volume and urinary sodium) and plasma and urinary cGMP were measured and compared to sodium restriction with out ANF infusion. At the end of HS and LS periods, the response of pla sma aldosterone to angiotensin-II infusion was tested. ANF infusion pr evented the fall in plasma ANF from a mean of 17.7 on HS to 7 pmol/L o n LS by raising the level to 16.1 pmol/L. Cumulative negative sodium b alance and the rise in renin activity and aldosterone were almost iden tical in both parts of the experiment. There was a transient diuretic and mild hypotensive effect of ANF. Plasma and urinary cGMP rose only transiently during ANF infusion despite constantly elevated ANF levels , suggesting that the effect of ANF was blunted under long term condit ions by receptor down-regulation or other mechanisms inhibiting cGMP f ormation. Chronic ANF infusion did not blunt the enhanced aldosterone response to angiotensin-II in the LS state. ANF does not seem to play a major role in the long term renal and hormonal adaptation to dietary sodium restriction.