HUMAN LEPTIN HAS NATRIURETIC ACTIVITY IN THE RAT

The purpose of this study was to determine whether leptin influences r enal function. Increasing doses (0.3, 1, 3, 10, and 30 mu g/min; 30 mi n per dose) of human leptin (h-leptin) infused into the renal artery o f anesthetized rats caused a twofold increase (P < 0.01) in urine volu me (UV), sodium excretion rate (UNaV), and the ratio of UNaV to potass ium excretion rate (UKV) from the ipsilateral kidney but had no effect on arterial blood pressure, renal blood flow, glomerular filtration r ate, or UKV. Mouse leptin was inactive in the rat. In a second study, a single dose of h-leptin (30 mu g/min) infused into the renal artery caused a significant twofold increase in UV and UNaV from the ipsilate ral but not contralateral kidney and revealed a time lag (similar to 1 .5 h) in the measurable response. In a third study, single doses of h- leptin were infused into the renal artery of four groups of rats (0.3, 1, 3, and 10 mu g/min) for 140 min. The ratio of UNaV to UKV from the ipsilateral kidney was significantly increased by all doses of h-lept in. We conclude that h-leptin may function as a potassium-sparing diur etic/natriuretic factor.