Human leptin administered intraperitoneally stimulates natriuresis and decreases renal medullary Na+, K+-ATPase activity in the rat -- impaired effect in dietary-induced obesity.
BACKGROUND
Leptin, produced by adipose tissue, apart from regulating food intake and energy expenditure, also has natriuretic activity. In this study we examined the effect of leptin on renal Na+, K+-ATPase responsible for active tubular sodium reabsorption, and compared the renal effects of leptin in lean and obese rats.


METHODS
Male Wistar rats were either kept on normal laboratory chow or made obese by a high-calorie diet. The animals were placed in metabolic cages and urine was collected in 2-hour periods.


RESULTS
In lean animals, leptin (1 mg/kg i.p.) caused a 139.5% increase in urine output, a 112.4% increase in natriuresis, and a 57.2% increase in the fractional excretion of sodium, but had no effect on the glomerular filtration rate. Leptin at this dose decreased renal medullary Na+, K+-ATPase activity at 30 minutes, 1 hour and 2 hours by 31%, 34.3% and 21.2%, respectively. The effect of leptin on Na+, K+-ATPase at 1 hour was dose-dependent; the lowest dose inducing significant inhibition was 0.25 mg/kg. By contrast, leptin had no effect on either cortical Na+, K+-ATPase or the ouabain-resistant fraction of ATPase. In obese rats, leptin increased urine output by only 29.1% and natriuresis by 28.9%, and had no significant effect on medullary Na+, K+-ATPase.


CONCLUSIONS
Leptin stimulates natriuresis primarily by inhibiting tubular sodium reabsorption. This effect is mediated, at least partially, by decreased Na+, K+-ATPase activity in the renal medulla, and is impaired in obese rats.
Bełtowski
Jerzy
J
Department of Pathophysiology, Lublin Medical University, Lublin, Poland. patfiz@asklepios.am.lublin.pl
W jcicka
Grazyna
G
Górny
Dionizy
D
Marciniak
Andrzej
A
D000818:Animals; D001794:Blood Pressure; D004032:Diet; D006801:Humans; D007274:Injections, Intraperitoneal; D007679:Kidney Medulla / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D020738:Leptin / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009318:Natriuresis / Q000187:drug effects*; D009765:Obesity / Q000201:enzymology* / Q000209:etiology / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*
D020738:Leptin; D000254:Sodium-Potassium-Exchanging ATPase