Natriuresis induced by mild hypernatremia in humans

Andersen, Lotte Bøgh; Andersen, Jens V.; Pump, Bettina; Bie, Peter

doi:10.1152/ajpregu.00732.2001

Cited by 58 publications

(72 citation statements)

References 45 publications

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“…However, interventional studies in healthy humans with acute salt loading or longer lasting salt diets do not corroborate this hypothesis. Thus, slow salt loading by an infusion of saline markedly suppressed PRA without any detectable changes in the arterial blood pressure [82] or even a slight decrease in blood pressure in humans [2]. Similarly, PRC was reduced by a saline infusion in dogs without any detectable changes in MABP [9].…”

Section: Regulation Of the Renin System By Salt-dependent Changes In mentioning

confidence: 89%

Salt feedback on the renin-angiotensin-aldosterone system

Schweda

2014

Pflugers Arch - Eur J Physiol

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The renin-angiotensin-aldosterone system (RAAS) is a central element in the control of the salt and water balance of the body and arterial blood pressure. The activity of the RAAS is controlled by the protease renin, which is released from renal juxtaglomerular epithelioid cells (JGE cells) into the circulation. Renin release is regulated by a complex interplay of several locally acting hormones or mechanisms and longer feedback loops one of which involves salt intake. Acute NaCl loads or longer lasting high salt intakes suppress plasma renin activity, whereas reductions in NaCl intake stimulate it. Because the activation of the RAAS conserves the salt content of the body, a classical feedback loop between salt intake/body salt content and renin is established. Despite of its important role for body fluid homeostasis, the precise signaling pathways connecting salt intake with the synthesis and release of renin are only incompletely understood. Four putative controllers of the salt-dependent regulation of the RAAS have been suggested: (1) the macula densa mechanism which adjusts renin release in response to changes in the renal tubular salt concentration; (2) salt-dependent changes in the arterial blood pressure; (3) circulating salt-dependent hormones, particularly the atrial natriuretic peptide (ANP); and (4) renal sympathetic nervous activity, which is regulated by extracellular volume and arterial blood pressure. In this review, the role of these known controllers of the RAAS will be discussed with special emphasis on their relative contributions to the salt-dependent regulation of the RAAS at different time frames.

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Section: Regulation Of the Renin System By Salt-dependent Changes In mentioning

confidence: 89%

Salt feedback on the renin-angiotensin-aldosterone system

Schweda

2014

Pflugers Arch - Eur J Physiol

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“…However, there is evidence of blood pressure-independent natriuresis and regulation of the renin system (21-24, 353, 746, 747). It has been found that acute salt loading, either by isotonic or hypertonic solutions, was followed by natriuresis without changes in blood pressure, and in one study, this effect even occurred together with a fall in blood pressure (22). These findings suggest that the response to sodium load may take place in the absence of increases in blood pressure, and therefore, the pressure-natriuresis concept may be inadequate (75).…”

Section: B Salt Intakementioning

confidence: 95%

Physiology of Kidney Renin

Castrop

Höcherl

Kurtz

et al. 2010

Physiological Reviews

232

277

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The protease renin is the key enzyme of the renin-angiotensin-aldosterone cascade, which is relevant under both physiological and pathophysiological settings. The kidney is the only organ capable of releasing enzymatically active renin. Although the characteristic juxtaglomerular position is the best known site of renin generation, renin-producing cells in the kidney can vary in number and localization. (Pro)renin gene transcription in these cells is controlled by a number of transcription factors, among which CREB is the best characterized. Pro-renin is stored in vesicles, activated to renin, and then released upon demand. The release of renin is under the control of the cAMP (stimulatory) and Ca2+(inhibitory) signaling pathways. Meanwhile, a great number of intrarenally generated or systemically acting factors have been identified that control the renin secretion directly at the level of renin-producing cells, by activating either of the signaling pathways mentioned above. The broad spectrum of biological actions of (pro)renin is mediated by receptors for (pro)renin, angiotensin II and angiotensin-( 1 – 7 ).

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“…This response, termed dehydration natriuresis (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11), plays an important role in preventing further accentuation of hypernatremia and the accompanying rise in extracellular tonicity. A similar natriuresis is seen following infusion of hypertonic saline (12).…”

Section: Introductionmentioning

confidence: 99%

Tonicity-dependent induction of Sgk1 expression has a potential role in dehydration-induced natriuresis in rodents

Chen¹,

Grigsby²,

Law³

et al. 2009

J. Clin. Invest.

202

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In various mammalian species, including humans, water restriction leads to an acute increase in urinary sodium excretion. This process, known as dehydration natriuresis, helps prevent further accentuation of hypernatremia and the accompanying rise in extracellular tonicity. Serum-and glucocorticoid-inducible kinase (Sgk1), which is expressed in the renal medulla, is regulated by extracellular tonicity. However, the mechanism of its regulation and the physiological role of hypertonicity-induced SGK1 gene expression remain unclear. Here, we identified a tonicity-responsive enhancer (TonE) upstream of the rat Sgk1 transcriptional start site. The transcription factor NFAT5 associated with TonE in a tonicity-dependent fashion in cultured rat renal medullary cells, and selective blockade of NFAT5 activity resulted in suppression of the osmotic induction of the Sgk1 promoter. In vivo, water restriction of rats or mice led to increased urine osmolality, increased Sgk1 expression, increased expression of the type A natriuretic peptide receptor (NPR-A), and dehydration natriuresis. In cultured rat renal medullary cells, siRNA-mediated Sgk1 knockdown blocked the osmotic induction of natriuretic peptide receptor 1 (Npr1) gene expression. Furthermore, Npr1 -/-mice were resistant to dehydration natriuresis, which suggests that Sgk1-dependent activation of the NPR-A pathway may contribute to this response. Collectively, these findings define a specific mechanistic pathway for the osmotic regulation of Sgk1 gene expression and suggest that Sgk1 may play an important role in promoting the physiological response of the kidney to elevations in extracellular tonicity. IntroductionPersistent hypertonicity, typically reflecting a high extracellular sodium concentration, stresses mammalian cells due to the ensuing osmotic efflux of water that shrinks the cells and concentrates their contents. Under most conditions, the concentration of extracellular sodium in mammals is controlled primarily through regulation of water metabolism. As extracellular sodium and plasma tonicity rise, the thirst mechanism is activated, and secretion of the neurohypophyseal hormone vasopressin into plasma increases. Vasopressin binds to its cognate receptors in the collecting duct of the kidney, resulting in increased water retention.Following short-term water restriction, several mammals demonstrate an acute increase in urinary sodium excretion that is independent of changes in water metabolism. This response, termed dehydration natriuresis (1-11), plays an important role in preventing further accentuation of hypernatremia and the accompanying rise in extracellular tonicity. A similar natriuresis is seen following infusion of hypertonic saline (12). Investigations to date have suggested a role for central versus peripheral osmoreceptors and blood-borne versus neural effectors in contributing to dehydration-induced natriuresis; however, the precise mechanism(s) underlying this natriuresis remains undefined.

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Natriuresis induced by mild hypernatremia in humans

Cited by 58 publications

References 45 publications

Salt feedback on the renin-angiotensin-aldosterone system

Salt feedback on the renin-angiotensin-aldosterone system

Physiology of Kidney Renin

Tonicity-dependent induction of Sgk1 expression has a potential role in dehydration-induced natriuresis in rodents

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