up(4) A has direct biphasic effects on vascular smooth muscle of the mouse aorta but vasoconstriction dominates at low concentrations. In conscious rodents, step-up infusions of Up(4) A elicit hypotension and electrolyte retention.

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 ...

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It was hypothesized that the renal nerve activity (RNA) mediates the natriuretic response to an infusion of NaCl, which does not change mean arterial blood pressure (MABP). This was tested in trained rats supplied with appropriate chronic instrumentation. NaCl solution (1 M) was infused i.v. at 0.02 ml/min/kg (4–5 μl/min) for 2 h during measurements of circulatory, endocrine, and renal variables including RNA. During NaCl infusion RNA decreased by 15% (p<0.05) within 30 min of infusion and reached a nadir of −25% (p<0.05). Renal denervation per se decreased MABP by 15.5 mmHg (p<0.01). In sham operated rats, NaCl infusion increased plasma Na+ by 1.6 mmol/l (repeated measures ANOVA, p<0.03) but left MABP unchanged while heart rate (HR) decreased (455±7 to 427±7 bpm, p<0.0001). Urine flow tended to increase (p=0.056); sodium excretion increased 4‐fold (1.4±0.2 to 6.0±0.6 μmol/min, p<0.0001) while potassium excretion remained stable (2.2±0.3 to 2.3±0.4 μmol/min). NaCl infusion to renally denervated rats decreased HR similarly (423±17 to 393±20 bpm, p<0.005). In contrast, however, sodium excretion remained constant (2.2±0.8 to 3.9±0.9, p=0.68) despite a significant increase in MABP (102±3 to 109±3 mmHg, p<0.0001). It is concluded that a physiological sodium load increases sodium excretion by mechanisms dependent on renal nerves.Supported by the Danish Medical Research Council and the Novo Nordisk Foundation.

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