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

Abstract

The hemodynamic, hormonal, and renal excretory effects of intravenous bolus administration of synthetic murine leptin were examined in groups of anesthetized normotensive (Sprague-Dawley), hypertensive (spontaneously hypertensive), and both lean and obese Zucker rats. In the normotensive animals ( n = 8) an intravenous bolus of 400 μg/kg of leptin produced a significant six- to sevenfold elevation in sodium excretion compared with controls ( n = 8). The onset of natriuresis was delayed for ∼30–45 min. Mean arterial pressure (MAP), creatinine clearance, plasma renin activity (PRA), and plasma aldosterone concentration (PAC) remained unchanged. In contrast, the hypertensive rats were refractory to the natriuretic effects of leptin when infused either with 400 ( n = 8) or 1,600 ( n = 8) μg/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-Dawley animals, the natriuretic effect of the hormone was attenuated in the obese Zucker groups. At 400 μg/kg ( n = 8) no natriuresis was elicited, but at 1,600 μg/kg ( n = 8) a modest but significant two- to threefold increment in sodium excretion was observed in the obese rats. In both Zucker groups, MAP, creatinine clearance, PRA, and PAC were unchanged. Collectively, these results demonstrate a significant natriuretic effect of exogenous leptin in the normal rat and a blunted saluretic response in hypertension and obesity. It is suggested that leptin may be a potential salt-excretory factor in normal rats and may function pathophysiologically in obesity and hypertension.

The role of falling leptin levels in the neuroendocrine and metabolic adaptation to short-term starvation in healthy men

“…Fasting did significantly increase PRA and aldosterone, however, but r-metHuLeptin did not alter these fasting-induced changes in the mineralocorticoid axis. These findings are in contrast to the effect of leptin administration on increase natriuresis (49,50) and sympathetic activity (51) in normal, nonobese leptin-resistant Zucker rats (51). Our findings are in agreement with a previous study in nonobese men on an isocaloric diet in whom leptin administration (0.3 mg/kg per day) for 6 days had no effect on autonomic activity or urinary catecholamines (52).…”

Leptin Might be a Regulator of Serum Uric Acid Concentrations in Humans

“…In light of previous studies, 22,[32][33][34][35][36][37] there appears to be an intimate relationship through increased proximal tubular sodium reabsorption among high serum urate, resistance to the facilitatory effects of leptin on insulin sensitivity and renal sodium excretion, sympathetic hyperactivity, and hyperinsulinemia. In conclusion, our study is the first comprehensive and the largest study of the relationship between serum leptin and uric acid concentrations to date and suggests that leptin could be the missing link between obesity and hyperuricemia.…”

Physiology of Kidney Renin

“…Reports of a positive correlation between leptin and PRA in obesity and essential hypertension in humans suggest a potential role for leptin in renin release (5,836,894), but up to now, no direct effect of leptin on the release of renin from the kidney has been reported. In contrast, the carotid artery or intravenous infusion of leptin did not alter PRA in rats (793,914). However, leptin may indirectly induce renin release via a central activation of the renal sympathetic nervous system (120, 323,561,711,712,910).…”

“…Later on, it was observed that leptin also influences the cardiovascular and renal functions and that the increased levels of leptin in obesity may contribute to obesity-induced hypertension. It has been found, for example, that the infusion of leptin activates sympathetic nerve activity and increases the mean arterial blood pressure, heart rate, urine volume, and sodium excretion in rats (323,389,793,914). Reports of a positive correlation between leptin and PRA in obesity and essential hypertension in humans suggest a potential role for leptin in renin release (5,836,894), but up to now, no direct effect of leptin on the release of renin from the kidney has been reported.…”