Effect of chronic infusion of atrial natriuretic factor on plasma and urinary aldosterone, plasma renin activity, blood pressure and sodium excretion in 2-K, 1-C hypertensive rats.

Conscious two-kidney, one-clip (2-K, 1-C) hypertensive rats and their normotensive sham-operated controls were infused during 13 days with synthetic ANF (Arg 101 - Tyr 126) at 35 pmol/hr/rat by means of osmotic minipumps connected to the jugular vein. The initial blood pressure of 186 +/- 6 mmHg maximally decreased to 118 +/- 7 mmHg at day 5 and slowly rose afterwards without reaching basal values. A concomitant drop in pressure natriuresis and diuresis was observed. No changes were observed in ANF-infused sham-operated rats. Urinary aldosterone excretion declined in ANF-treated rats from a basal value of 63.38 +/- 21.04 micrograms/24 hr to 13.36 +/- 3.78 micrograms/24 hr the last infusion day. No change in urinary aldosterone was observed in either non-infused 2-K, 1-C or ANF-infused sham-operated rats. Plasma aldosterone was significantly higher only in non-treated 2-K, 1-C rats. Renal aldosterone clearance was significantly lower in ANF-infused 2-K, 1-C rats than in the other experimental groups. Plasma renin activity (PRA) was lower in treated (3.92 +/- 2.26 AI ng/ml/hr) than in non-treated (9.08 +/- 2.32 AI ng/ml/hr) hypertensive rats, and not different from ANF-infused or non-infused sham-operated rats. No differences in body weight between infused and non-infused rats, or hematocrit between any group were observed. Atrial immunoreactive ANF was not different in any group. These results demonstrate that chronic administration of ANF not only reduces blood pressure and PRA in 2-K, 1-C hypertensive rats but also plasma and urinary aldosterone. Whether the latter is a direct inhibitory effect or secondary to the normalization of PRA is not known. The hypotensive response may be due to a direct effect on vascular smooth muscle but a role of renin cannot be excluded. Because blood pressure returned toward basal values during the last days of the observation period, the possibility of a tachyphylactic effect of ANF on vascular smooth muscle cannot be excluded.