Renal nerves and the development of Dahl salt-sensitive hypertension.

Abstract

SUMMARY Several experimental forms of hypertension require intact renal innervation for the development or maintenance (or both) of the elevated arterial pressure. We determined the relationships between urinary sodium and water excretion and arterial pressure in Dahl salt-sensitive rats (DS) with innervated (n = 6) and denervated (n = 7) kidneys after switching from a low to a high sodium diet. Arterial pressure significantly increased in both groups within 48 hours after they began to eat an 8% sodium chloride diet. This hypertension increased to 188 ± 9 and 190 ± 7 mm Hg, respectively, in rats with innervated and denervated kidneys after 12 days. Mean arterial pressures were not significantly different between groups on any day. The rise in arterial pressure of DS placed on a high sodium intake was associated with an elevation of urine flow rate and urinary sodium excretion in rats with either innervated or denervated kidneys. Urine flow rates and urinary sodium excretions were greater in denervated than in innervated rats on Days 4 through 7 after beginning the high sodium diet. This diuresis and natriuresis in rats with denervated kidneys were associated with greater water and sodium intakes on Days 4 to 7 of the high sodium diet when compared with rats with innervated kidneys. These results demonstrate that, following exposure to a high sodium intake, DS have increased arterial pressure within 24 hours. The development of this arterial hypertension is not dependent on intact renal innervation. In conscious DS, the renal innervation does participate in the regulation of urinary sodium excretion by promoting renal sodium and water reabsorption. However, DS with either innervated or denervated kidneys maintained sodium balance and rapidly became hypertensive when fed a high salt diet. Thus, elevation of sodium intake in DS results in arterial hypertension independent of measurable renal neurogenic alterations in salt and water balance. 1 " 7 In these studies, renal denervation was shown to either abolish 2 ' 6i 7 or reduce the magnitude 13 " 5 of the hypertension. Alterations in the development of hypertension by renal denervation may result from interruption of renal afferent or renal efferent sympathetic pathways. Stimulation of renal afferent pathways has been reported to be important in the development of hypertension during ipsilateral renal artery stenosis 8 or during intrarenal infusion of adenosine.9 Activation of renal efferent nerve fibers either by direct electrical stimulation or by reflex activation of sympathetic outflow increases renal vascular resistance, tubular sodium reabsorption, and renin release. 10 These factors could elevate arterial pressure through the vasoconstrictor effects of subsequent increases in circulating angiotensin II or by expansion of the extracellular fluid volume through increased sodium and water reabsorption (or by both mechanisms).Abnormalities in neural control mechanisms of hypertensive animals have been reported, including prehypertensive Dahl salt-sensitive rat...

Renal Denervation Prevents and Reverses Hyperinsulinemia-Induced Hypertension in Rats

“…It has been demonstrated that renal denervation prevents or attenuates some forms of genetic and experimental hypertension in animals such as spontaneously hypertensive rats, 22,23 New Zealand genetically hypertensive rats, 24 2-kidney models of Goldblatt hypertensive rats, 25 lowsodium, 1-kidney hypertensive rats, 26 angiotensin-induced hypertensive rats, 27 and obesity-induced hypertensive dogs, 28 although negative results were reported in Dahl salt-sensitive rats 31 and Lyon hypertensive rats 32 and conflicting results were also obtained in hypertensive models induced by aortic coarctation, 33,34 NO synthase inhibition, 35,36 and deoxycorticosterone acetate salt treatment 37,38 and in the 1-kidney model of Goldblatt hypertensive rats. 39,40 In the present study, bilateral RD depleted the renal tissue NE content by 94% (measured at the end of the experiments, ie, 2 to 4 weeks after RD), suggesting that the denervation procedure was effective and that significant reinnervation had not yet occurred.…”

Role of the epithelial sodium channel in salt-sensitive hypertension

“…Previous studies have suggested that DS rats have abnormalities in the sympathetic nervous system (SNS) [88,89] and endothelial function [90,91] , which causes significant vascular resistance. In addition, there is evidence that supports the hypothesis that abnormal modulation of SNS is involved in www.nature.com/aps Sun Y et al Acta Pharmacologica Sinica npg salt-inducd hypertension.…”

Renal Intramedullary Infusion of l -Arginine Prevents Reduction of Medullary Blood Flow and Hypertension in Dahl Salt-Sensitive Rats

“…22 Yet, it was found that renal denervation of Dahl S rats did not slow the onset or the degree of hypertension in Dahl S rats. 23 Alternatively, the greater increase of CSF Na concentrations in Dahl S rats could lead to the reported greater elevations of plasma arginine vasopressin (AVP) in Dahl S rats compared with Dahl R rats. 22 We have shown that small physiological elevations of plasma AVP can significantly reduce MBF and blunt the acute pressurenatriuresis relationship, 24 so it is possible that AVP could account for reduced medullary perfusion in Dahl S rats with high salt intake.…”