DOSE-RESPONSE ANALYSIS OF ACUTE HYPOTENSIVE AND RENAL EFFECTS OF ATRIAL-NATRIURETIC-PEPTIDE IN THE RAT

Acute treatments with synthetic atrial natriuretic peptides induce hyp otension, in which several mechanisms, including renal effects, are in volved. The implication of the renal vasculature and the excretory cap acities in the hypotensive action of atrial natriuretic peptides are n ot ascertained as yet. To address this issue, the rapid time sequence of the acute effects of atrial natriuretic peptides upon renal blood f low, mean arterial pressure, heart rate, and salt and water excretion, as well as a dose-response analysis, were investigated in 38 anesthet ized euvolemic rats. Doses varying from 0.25 to 2.50 mu g of atrial na triuretic peptide were injected i.v. in 30 sec. Each dose induced a br isk and transient increase in renal blood flow, which was maximal (13 %) above 1 mu g of atrial natiuretic peptide. A small reduction in mea n arterial pressure, timely related to renal vasodilatation, occurred at first. It was followed by a second reduction in mean arterial press ure, which was concomitant to the maximal increases in diuresis and na triuresis. It persisted over a longer period of time. The maximal hypo tensive effect (-15 mmHg) was observed above 1.5 mu g of atrial natiur etic peptide. All effects were dose-dependent. There were no changes i n heart rate. In conclusion, atrial natiuretic peptides transiently in duced dose-dependent increases in renal blood flow and salt and water excretion, while the mean arterial pressure decreased stepwisely. The biphasic hypotensive effect was time-related to the renal vasodilator and diuretic effects, respectively.