Inhibition of atrial natriuretic peptide-induced natriuresis by plasma hydrolysates containing pepsanurin.

Abstract

The specificity of antidiuretic actions of pepsanurin, a peptidic fraction obtained by pepsin hydrolysis of plasma, was studied in anesthetized rats and in isolated perfused rat kidneys. Pepsanurin was obtained from fresh dialyzed human plasma digested with pepsin (2,400 units/ml, 18 hours at 37 degrees C, pH 2.5), deproteinized (10 minutes at 80 degrees C), and centrifuged. In the rat, intraperitoneal injections of pepsanurin (0.5 ml/100 g body wt) significantly inhibited the effects of an intravenous bolus of atrial natriuretic peptide (ANP) (0.5 micrograms) on water, sodium, and potassium excretion without altering systemic blood pressure. In addition, pepsanurin abolished the peak in glomerular filtration rate and reduced the ANP-induced rise in fractional sodium excretion. Pepsanurin also inhibited the natriuretic effects of amiloride (10 micrograms/100 g body wt i.v.) without changing glomerular filtration rate, but it did not inhibit the potassium-retaining effect of amiloride. In contrast, pepsanurin had no effect on basal urinary excretion, and it did not affect the diuretic response induced by furosemide (doses of 25, 50, or 100 micrograms i.v.). Control peptidic hydrolysates prepared from human plasma preincubated 48 hours at 37 degrees C (PIPH), bovine albumin (BSAH), or human albumin did not inhibit ANP, amiloride, or furosemide. In perfused kidneys, pepsanurin significantly and reversibly reduced sodium and water excretion. Furthermore, pepsanurin, but not PIPH or BSAH, blocked the natriuretic and diuretic effects of ANP. These results support the existence of a specific plasma substrate able to release a peptide or peptides that counteract distal tubule diuresis and natriuresis by an intrarenal mechanism.