RT Journal Article SR Electronic T1 Kinetics and pharmacodynamics of atrial natriuretic peptide and lithium clearance in the isolated perfused rat kidney. JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 868 OP 873 VO 243 IS 3 A1 M E Brier A1 R A Brier A1 F C Luft A1 G R Aronoff YR 1987 UL http://jpet.aspetjournals.org/content/243/3/868.abstract AB We used the kinetics of atrial natriuretic peptide (ANP) and fractional lithium excretion to test the hypothesis that ANP-induced natriuresis is related directly to the ANP perfusate concentration and is mediated by a decrease in proximal tubular sodium reabsorption. Wistar rat kidneys were perfused for 90 min after administration of 1 microgram of human ANP. Comparisons were made to control perfusions. ANP had a short half-life (12.4 min) and a renal clearance 6-fold greater than the creatinine clearance. ANP treatment resulted in a significant peak increase in sodium (5.6-fold), lithium (2.1-fold), potassium (2.3-fold) and water (5.1-fold) excretion. The natriuretic response to ANP was delayed 25 min. Exogenous creatinine clearance, perfusion pressure, perfusion flow and renal vascular resistance were not affected. We conclude that the kidney eliminates ANP rapidly by mechanisms that appear to be located primarily in the peritubular circulation. The initial renal response to ANP did not follow perfusate concentrations. Rather, natriuresis increased as ANP concentrations decreased. The relationship was defined by a counterclockwise hysteresis loop. Natriuresis was not mediated by an increased delivery of sodium to the tubule, but may have been due to either a direct or an indirect action of ANP on the kidney.