Effects of chronic nitric oxide inhibition on the renal excretory response to leptin

Objective: Previous investigations have demonstrated that leptin promotes natriuresis with a renal tubular effect. However, the mechanisms involved in this response are unclear. The present study was designed to examine the hypothesis that the natriuretic response to leptin in normotensive Sprague-Dawley rats is regulated by nitric oxide (NO). Research Methods and Procedures: The hemodynamic and renal excretory effects of intravenous bolus administration of pharmacological doses of synthetic murine leptin were examined in groups of control Sprague-Dawley rats (n = 8), Sprague-Dawley rats treated for 4 days with the NO synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME) (n = 8), and Sprague-Dawley rats treated for 4 days with L-NAME followed by acute treatment with sodium nitroprusside (n = 8). Results: In the control group (n = 8), an intravenous bolus of leptin, 400 mug/kg body weight, increased urinary sodium excretion 4- to 6-fold. In the Sprague-Dawley rats chronically administered L-NAME (n = 8), an intravenous bolus of 400 mug/kg of leptin did not increase sodium excretion. Acute sodium nitroprusside infusion to Sprague-Dawley rats chronically treated with L-NAME (n = 8) was associated with partial restoration of the sodium excretory response to leptin administration. Discussion: Collectively, these results are interpreted to suggest that the natriuretic and diuretic responses to leptin observed in the Sprague-Dawley rat require a functional NO system.