Effects of uroguanylin on natriuresis in experimental nephrotic rats

Abstract

Uroguanylin, isolated from human and opossum urine, is a candidate intestinal natriuretic hormone that controls the sodium and water balance between the intestine and the kidneys. Levels of immunoreactive (ir)-uroguanylin in the plasma and urine are increased in rats and humans with nephrotic syndrome, which is physiologically characterized by sodium retention with massive proteinuria. The present study evaluates the effect of natriuresis induced by uroguanylin on nephrotic rats. Normal rats and rats rendered nephrotic by injections of puromycin aminonucleoside (PAN) were treated with uroguanylin (0.5 nmol/h, delivered by an osmotic pump) or with vehicle during the sodium retention phase. All rats consumed the same quantity of sodium. Uroguanylin did not increase urinary excretion of sodium and water in normal rats, but significantly increased urinary sodium excretion during the sodium retention phase in nephrotic rats (untreated vs uroguanylin-treated nephrotic rats in mmol/mmol creatinine; 2.92 +/- 0.65 vs 8.93 +/- 2.53 on day 6, P < 0.05; 3.55 +/- 0.47 vs 10.37 +/- 1.73 on day 7, P < 0.01; 14.88 +/- 2.32 vs 24.47 +/- 2.86 on day 8, P < 0.05). Plasma levels of ir-uroguanylin in uroguanylin-treated nephrotic rats on day 6 were significantly increased compared with those in uroguanylin-treated control and untreated nephrotic rats. Uroguanylin increased urinary sodium excretion in rats with PAN-induced nephrosis, and might be useful for treating sodium retention in patients with nephrotic syndrome.