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

Abstract

Kompanowska-Jezierska E, Wolff H, Kuczeriszka M, Gramsbergen JB, Walkowska A, Johns EJ, Bie P. Renal nerves and nNOS: roles in natriuresis of acute isovolumetric sodium loading in conscious rats. Am J Physiol Regul Integr Comp Physiol 294: R1130-R1139, 2008. First published January 30, 2008 doi:10.1152/ajpregu.00908.2007.-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 mol ⅐ min Ϫ1 ⅐ kg body mass Ϫ1 ) at constant body volume conditions. SMTC was coinfused in amounts (20 g ⅐ min Ϫ1 ⅐ kg Ϫ1 ) reported to selectively inhibit nNOS. Directly measured MABPs of acutely and chronically denervated rats were less than control (15% and 9%, respectively, P Ͻ 0.005). Plasma renin concentration (PRC) was reduced by renal denervation (14.5 Ϯ 0.2 vs. 19.3 Ϯ 1.3 mIU/l, P Ͻ 0.005) and by nNOS inhibition (12.4 Ϯ 2.3 vs. 19.6 Ϯ 1.6 mlU/l, P Ͻ 0.005). NaLoad reduced PRC (P Ͻ 0.05) and elevated MABP modestly (P Ͻ 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 Ͻ 0.001). These data show that renal denervation decreases MABP and renin secretion. However, neither renal denervation nor nNOS inhibition affects either the renin downregulation 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 THE INTERRELATIONSHIP BETWEEN blood pressure changes and acute variations in water and sodium excretion is not well defined. Arterial blood pressure is controlled by multiple systems, which differ widely in their time of activation. Neural systems react within seconds, while the hormonal and paracrine systems are more sluggish, requiring minutes to hours, or even days, to respond with full capacity. Neurogenic factors have long been hypothesized to be important in the initiation and maintenance of high blood pressure. There is considerable evidence suggesting that enhanced sympathetic drive to the heart and peripheral circulation is involved in the development of persistent blood pressure elevation or maintains the blood pressure elevation originally induced by nonneurogenic mechanisms (11). Moreover, it is known that electrical stimulation of the renal ...

Normotensive sodium loading in normal man: regulation of renin secretion during β-receptor blockade

“…Recent studies in conscious rats may provide suggestions in this regard. Renal denervation did not affect the renin inhibitory or natriuretic responses to a sodium load (50 mol⅐kg Ϫ1 ⅐min Ϫ1 ), which elicited a slight increase (5)(6)(7)(8) in MAP (21), compatible with the notion that RSNA plays only a minor role when MAP increases measurably. However, preliminary results have shown 1) that a lower infusion rate (20 mol⅐kg Ϫ1 ⅐min Ϫ1 ), which did not change MAP, nevertheless reduced RSNA (measured by implanted electrodes) and 2) that the natriuresis induced by this sodium load was eliminated by renal denervation (7).…”

Role of the afferent renal nerves in sodium homeostasis and blood pressure regulation in rats

“…(Kompanowska-Jezierska et al, 2008;Wainford et al, 2013). Following the 2 h recovery period, conscious rats were challenged with an acute 1 M NaCl infusion protocol consisting of a 1 h control period (isotonic saline, 20 µl min −1 , I.V.)…”

Physiology of Kidney Renin

“…In addition, it was shown that the natriuresis in response to sodium load, which increased blood pressure, was inhibited by the administration of ANG II, suggesting that a decrease in the RAS is a prerequisite for the natriuretic response to sodium load (21, 74). Subsequent elegant studies in humans and laboratory animals further suggest that the suppression of renin release in response to an acute modest sodium load is not only independent of changes in blood pressure, but also independent of cardiac output, GFR, ANP, ␤ 1 -adrenergic receptors, plasma sodium levels, osmolality, renal nerves, and nNOS-derived NO (73,456,593,717). Therefore, the question arises which mechanism(s) mediates natriuresis and suppression of renin in response to an acute modest sodium load.…”