EN
We examined the effect of leptin on renal function and renal Na+,K+-ATPase and ouabain-sensitive H+,K+-ATPase activities in the rat. Leptin was infused under general anaesthesia into the abdominal aorta proximally to the renal arteries. Leptin infused at doses of 1 and 10 µg/kg/min increased urine output by 40% and 140%, respectively. Urinary Na+ excretion increased in rats receiving leptin at doses of 0.1, 1, and 10 µg/kg/min by 57.6%, 124.2% and 163.6%, respectively. Leptin had no effect on creatinine clearance, potassium excretion and phosphate excretion. Na+,K+-ATPase activity in the renal medulla of rats treated with 1 and 10 µg/kg/min leptin was lower than in control animals by 25.5% and 33.2%, respectively. In contrast, cortical Na+,K+-ATPase as well as either cortical or medullary ouabain-sensitive H+,K+-ATPase activities did not differ between leptin-treated and control animals. The effect of leptin on Na+,K+-ATPase activity was abolished by actin depolymerizing agents, cytochalazin D and latrunculin B, and by phosphatidylinositol 3-kinase (PI3K) inhibitors, wortmannin and LY294002. These results indicate that: 1) natriuretic effect of leptin is mediated, at least in part, by decrease in renal medullary Na+,K+-ATPase activity, 2) inhibition of medullary Na+,K+-ATPase by leptin is mediated by PI3K and requires integrity of actin cytoskeleton.