Renal effects of leptin in normotensive, hypertensive, and obese rats

The hemodynamic, hormonal, and renal excretory effects of intravenous bolus administration of synthetic murine leptin were examined in groups of anest hetized normotensive (Sprague-Dawley), hypertensive (spontaneously hyperten sive), and both lean and obese Zucker rats. In the normotensive animals (n = 8) an intravenous bolus of 400 mu g/kg of leptin produced a significant s ix- to sevenfold elevation in sodium excretion compared with controls (n = 8). The onset of natriuresis was delayed for similar to 30-45 min. Mean art erial pressure (MAP), creatinine clearance, plasma renin activity (PRA), an d plasma aldosterone concentration (PAC) remained unchanged. In contrast, t he hypertensive rats were refractory to the natriuretic effects of leptin w hen infused either with 400 (n = 8) or 1,600 (n = 8) mu g/kg. Also in these animals MAP, creatinine clearance, PRA, and PAC were unmodified. Finally, whereas lean Zucker rats (n = 8) responded very similarly to the Sprague-Da wley animals, the natriuretic effect of the hormone was attenuated in the o bese Zucker groups. At 400 mu g/kg (n = 8) no natriuresis was elicited, but at 1,600 mu g/kg(n = 8) a modest but significant two- to threefold increme nt in sodium excretion was observed in the obese rats. In both Zucker group s, MAP, creatinine clearance, PRA, and PAC were unchanged. Collectively, th ese results demonstrate a significant natriuretic effect of exogenous lepti n in the normal rat and a blunted saluretic response in hypertension and ob esity. It is suggested that leptin may be a potential salt-excretory factor in normal rats and may function pathophysiologically in obesity and hypert ension.