Dual Action of Leptin on Renal Sodium Handling
BACKGROUND: Leptin exerts a natriuretic effect when infused directly into renal artery. However, in the conditions like obesity where circulating level of leptin is increased, this local effect may be opposed by centrally mediated stimulation of renal sympathetic nerve activity (RSNA). To investigate the interrelationship of the two factors, we made renal clearance study during intravenous leptin infusion in male Sprague-Dawley rats pretreated with unilateral renal denervation. METHODS: Rats were anesthetized with 50 mg/kg body weight (BW) intraperitoneal pentobarbital and supplementation with intravenous α-chloralose. Left renal vessels were isolated from surrounding tissue and applied with 10% phenol solution. Catheters were inserted into bladder and the proximal cut end of left ureter. Recombinant murine leptin was infused intravenously at 1 mg/kg BW over 3 hours. Renal function was assessed by timed collection of urine from each kidney and arterial blood under constant infusion of inulin. In another series of experiment, RSNA was recorded from left renal nerve and expressed as percent change from baseline. RESULTS: Mean blood pressure and heart rate were not affected by leptin. RSNA increased gradually by 45% at 105 min after leptin infusion and remained elevated. Glomerular filtration rates were 0.49±0.04 and 0.44±0.03 ml/min/100 gBW in intact and denervated kidney and both did not change significantly after leptin infusion. Urinary sodium excretion (UNaV) from the intact kidney was 527±42 nEq/min at baseline, increased to 1098±173 at 45 min, and returned to 606±82 nEq/min at 135 min after leptin infusion. Concomitant values from the denervated kidney were 898±105, 1822±272, and 1305±159 nEq/min, respectively. Thus, the ratio of UNaV from denervated to intact kidney increased significantly from 1.71±0.14 and 1.68±0.16 at baseline and 45 min to 2.27±0.30 at 135 min after leptin infusion. CONCLUSIONS: These results suggest that sodium balance after exogenous leptin infusion is determined by tubular effect and renal sympathetic nerve activity. Derangement of these factors may facilitate hypertension in obese subjects.