Effects of renal denervation on the sodium excretory actions of leptin in hypertensive rats

Abstract

Background. Previous studies from this laboratory have reported a marked attenuation of the renal responses to pharmacologic doses of synthetic murine leptin infused in the spontaneously hypertensive rat (SHR) model compared with normotensive Sprague-Dawley and lean Zucker rat models. Methods. In the present study, the hemodynamic and renal excretory effects of an intravenous bolus administration of pharmacologic doses of synthetic murine leptin were examined in groups of anesthetized SHR with unilateral nephrectomy and renal denervation or sham-denervation of the remaining kidney. Results. In the SHR with acute renal denervation (N = 8), an intravenous bolus of 1600 μg/kg of leptin produced a significant twofold to fourfold elevation in sodium excretion but did not increase natriuresis in the sham-denervated group (N = 6). Chronic renal denervation of one-week duration (N = 8) was associated with qualitatively and quantitatively similar increases of sodium excretion in response to leptin administration. Mean arterial pressure remained unchanged in all groups after the administration of leptin. Conclusions. Collectively, these results are interpreted to suggest that the blunted natriuretic and diuretic responses to leptin observed in the SHR with intact renal nerves may be partially explained by the antinatriuretic effect of an enhanced baseline efferent renal sympathetic activity and/or leptin's stimulation of the sympathetic nervous system.