Renal nerves and nNOS: roles in natriuresis of acute isovolumetric sodium loading in conscious rats

1 Department of Physiology and Pharmacology, University of Southern Denmark, Odense, Denmark; 2 Laboratory of Renal and Body Fluid Physiology, M. Mossakowski Medical Research Centre of the Polish Academy of Sciences, Warsaw, Poland; 3 Department of Anatomy and Neurobiology, University of Southern Denmark, Odense, Denmark; and 4 Department of Physiology, University College Cork, Cork, Republic of Ireland Submitted 20 December 2007 ; accepted in final form 21 January 2008 It was hypothesized that renal sympathetic nerve activity (RSNA) and neuronal nitric oxide synthase (nNOS) are involved in the acute inhibition of renin secretion and the natriuresis following slow NaCl loading (NaLoad) and that RSNA participates in the regulation of arterial blood pressure (MABP). This was tested by NaLoad after chronic renal denervation with and without inhibition of nNOS by S-methyl-thiocitrulline (SMTC). In addition, the acute effects of renal denervation on MABP and sodium balance were assessed. Rats were investigated in the conscious, catheterized state, in metabolic cages, and acutely during anesthesia. NaLoad was performed over 2 h by intravenous infusion of hypertonic solution (50 µmol·min –1 ·kg body mass –1 ) at constant body volume conditions. SMTC was coinfused in amounts (20 µg·min –1 ·kg –1 ) reported to selectively inhibit nNOS. Directly measured MABPs of acutely and chronically denervated rats were less than control (15% and 9%, respectively, P < 0.005). Plasma renin concentration (PRC) was reduced by renal denervation (14.5 ± 0.2 vs. 19.3 ± 1.3 mIU/l, P < 0.005) and by nNOS inhibition (12.4 ± 2.3 vs. 19.6 ± 1.6 mlU/l, P < 0.005). NaLoad reduced PRC ( P < 0.05) and elevated MABP modestly ( P < 0.05) and increased sodium excretion six-fold, irrespective of renal denervation and SMTC. The metabolic data demonstrated that renal denervation lowered sodium balance during the first days after denervation ( P < 0.001). These data show that renal denervation decreases MABP and renin secretion. However, neither renal denervation nor nNOS inhibition affects either the renin down-regulation or the natriuretic response to acute sodium loading. Acute sodium-driven renin regulation seems independent of RSNA and nNOS under the present conditions. plasma renin concentration; total body sodium; blood pressure; sodium excretion Address for reprint requests and other correspondence: P. Bie, Dept. of Physiology and Pharmacology, Univ. of Southern Denmark, 21 Winslowsvej, Rm. 3