Short-term nonpressor angiotensin II infusion stimulates sodium transporters in proximal tubule and distal nephron

Nguyen, Mien T. X.; Han, Jianbo; Ralph, Donna L.; Veiras, Luciana C.; McDonough, Alicia A.

doi:10.14814/phy2.12496

Cited by 41 publications

(50 citation statements)

References 43 publications

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“…40 In cultured kidney epithelial cells, NCC is rapidly trafficked to the cell surface in a phosphorylation-independent manner within minutes of an increase in AngII, then, after an hour, AngII induces SPAK-dependent NCC phosphorylation. 41 The time course of chronic treatment with AngII provides support for direct activation of NCC phosphorylation by AngII: in 3 day AngII- infused rats, NCC and NCCp increase 0.5-fold in the absence of increased ENaC activating cleavage, urinary K + loss or K + depletion; 42 as mentioned above, in 4 day AngII infused mice, SPAK and SPAKp increased significantly prior to NCC or NCCp increases in the same samples, suggesting that SPAK regulation precedes NCC regulation by AngII; 8 a key caveat is that potassium balance was not measured.…”

Section: Discussionmentioning

confidence: 99%

Potassium Supplementation Prevents Sodium Chloride Cotransporter Stimulation During Angiotensin II Hypertension

et al. 2016

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Ang II hypertension increases distal tubule Na-Cl cotransporter (NCC) abundance and phosphorylation (NCCp), as well as epithelial Na+ channel (ENaC) abundance and activating cleavage. Acutely raising plasma [K+] by infusion or ingestion provokes a rapid decrease in NCCp that drives a compensatory kaliuresis. The first aim tested whether acutely raising plasma [K+] with a single 3 hr 2% potassium meal would lower NCCp in Sprague Dawley rats after 14 days of AngII (400 ng/kg/min). The potassium-rich meal neither decreased NCCp nor increased K+ excretion. AngII infused rats exhibited lower plasma [K+] versus controls (3.6 ± 0.2 vs. 4.5 ± 0.1 mmol/L, p < 0.05) suggesting that Ang II mediated ENaC activation provokes K+ depletion. The second aim tested whether doubling dietary potassium intake from 1% (A1K) to 2% (A2K) would prevent K+ depletion during AngII infusion and, thus, prevent NCC accumulation. A2K fed rats exhibited normal plasma [K+] and 2-fold higher K+ excretion and plasma [aldosterone] versus A1K. In A1K rats, NCC, NCCpS71, and NCCpT53 abundance increased 1.5- to 3-fold versus controls (p< 0.05). The rise in NCC and NCCp abundance was prevented in the A2K rats, yet blood pressure did not significantly decrease. ENaC subunit abundance and cleavage increased 1.5- to 3-fold in both A1K and A2K; ROMK abundance was unaffected by Ang II or dietary K+. In summary, the accumulation and phosphorylation of NCC seen during chronic AngII infusion hypertension is likely secondary to potassium deficiency driven by ENaC stimulation.

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Section: Discussionmentioning

confidence: 99%

Potassium Supplementation Prevents Sodium Chloride Cotransporter Stimulation During Angiotensin II Hypertension

et al. 2016

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“…Although NHE3 expression and activity are regulated by a complex of vasoactive factors, ANG II is one of the most important factors [18, 89••, 164, 172–174, 175•]. We and others have consistently shown that ANG II induces NHE3 expression and increases NHE3 activity in cultured proximal tubule cells in vitro [89••, 130, 150, 159••, 176–179].…”

Section: Nhe3 As a Major Target Of Circulating Paracrine And Intracmentioning

confidence: 99%

“…We and others have consistently shown that ANG II induces NHE3 expression and increases NHE3 activity in cultured proximal tubule cells in vitro [89••, 130, 150, 159••, 176–179]. However, in vivo effects of ANG II on NHE3 activity in the proximal tubules of the kidney appear to be dose- and blood pressure-dependent [18, 89••, 175•, 180, 181, 182••]. We found that infusion of pressor doses of ANG II with rapid rise in blood pressure inhibited proximal tubule NHE3 and induced pressure natriuresis, whereas long-term infusion of subpressor doses of ANG II increased the expression and activity of NHE3 in proximal tubules and induced antinatriuretic responses [89••].…”

Section: Nhe3 As a Major Target Of Circulating Paracrine And Intracmentioning

confidence: 99%

“…ANG II-induced hypertension significantly decreased NHE3 abundance in the cortex as well as in the medulla, but significantly increased Na + /Cl − cotransporters (NCC) in the distal convoluted tubule and epithelial Na + channel subunits in both cortex and medulla [182••]. In the absence of the changes in blood pressure and/or GFR, low doses of ANG II infusion provoked multiple transporter proteins trafficking to brush border membranes [183] or increase NHE3 abundance in the proximal tubules [175•]. These studies indicate that at physiological or subpressor levels, ANG II increases NHE3 expression and activity in the proximal tubules of the kidney, contributing to normal blood pressure homeostasis.…”

Section: Nhe3 As a Major Target Of Circulating Paracrine And Intracmentioning

confidence: 99%

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Recent Updates on the Proximal Tubule Renin-Angiotensin System in Angiotensin II-Dependent Hypertension

Zhuo²

2016

Curr Hypertens Rep

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It is well recognized that the renin-angiotensin system (RAS) exists not only as circulating, paracrine (cell to cell), but also intracrine (intracellular) system. In the kidney, however, it is difficult to dissect the respective contributions of circulating RAS versus intrarenal RAS to the physiological regulation of proximal tubular Na+ reabsorption and hypertension. Here, we review recent studies to provide an update in this research field with a focus on the proximal tubular RAS in angiotensin II (ANG II)-induced hypertension. Careful analysis of available evidence supports the hypothesis that both local synthesis or formation and AT1 (AT1a) receptor-and/or megalin-mediated uptake of angiotensinogen (AGT), ANG I and ANG II contribute to high levels of ANG II in the proximal tubules of the kidney. Under physiological conditions, nearly all major components of the RAS including AGT, prorenin, renin, ANG I, and ANG II would be filtered by the glomerulus and taken up by the proximal tubules. In ANG II-dependent hypertension, the expression of AGT, prorenin, and (pro)renin receptors, and angiotensin-converting enzyme (ACE) is upregulated rather than downregulated in the kidney. Furthermore, hypertension damages the glomerular filtration barrier, which augments the filtration of circulating AGT, prorenin, renin, ANG I, and ANG II and their uptake in the proximal tubules. Together, increased local ANG II formation and augmented uptake of circulating ANG II in the proximal tubules, via activation of AT1 (AT1a) receptors and Na+/H+ ex-changer 3, may provide a powerful feedforward mechanism for promoting Na+ retention and the development of ANG II-induced hypertension.

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“…AngII has a biphasic effect on blood pressure; acutely applied pressure doses of AngII induce pressure natriuresis possibly via internalization of NHE3, 14, 15 whereas long-term application of subpressor doses of AngII increase NHE3 expression and blood pressure. 16–18 Vice versa, inhibiting angiotensin-converting enzyme induced a redistribution of NHE3 from enriched microvillar membranes to intermicrovillar membrane-enriched fractions. 19 The role of NHE3 is supported by recent studies using NHE3 −/− 20 and tgNHE3 −/− 21 mice that have an absence of AngII-induced hypertension.…”

Section: Introductionmentioning

confidence: 99%

Renal tubular NHE3 is required in the maintenance of water and sodium chloride homeostasis

Fenton

Poulsen

Chavez

et al. 2017

Kidney International

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The sodium/proton exchanger isoform 3 (NHE3) is expressed in the intestine and the kidney where it facilitates sodium (re)absorption and proton secretion. The importance of NHE3 in the kidney for sodium chloride homeostasis, relative to the intestine, is unknown. Constitutive tubule-specific NHE3 knockout mice (NHE3loxloxCre) did not show significant differences compared to control mice in body weight, blood pH or bicarbonate and plasma sodium, potassium or aldosterone levels. Fluid intake, urinary flow rate, urinary sodium/creatinine and pH were significantly elevated in NHE3loxloxCre mice while urine osmolality and GFR were significantly lower. Water deprivation revealed a small urinary concentrating defect in NHE3loxloxCre mice on a control diet; exaggerated on low sodium chloride. Ten days of low or high sodium chloride diet did not affect plasma sodium in control mice; however, NHE3loxloxCre mice were susceptible to low sodium chloride (about −4 mM) or high sodium chloride intake (about +2 mM) versus baseline, effects without differences in plasma aldosterone between groups. Blood pressure was significantly lower in NHE3loxloxCre mice and was sodium chloride-sensitive. In control mice, the expression of the sodium/phosphate co-transporter Npt2c was sodium chloride-sensitive. However, lack of tubular NHE3 blunted Npt2c expression. Alterations in the abundances of sodium/chloride cotransporter and its phosphorylation at threonine 58 as well as the abundances of the α-subunit of the epithelial sodium channel, and its cleaved form, were also apparent in NHE3loxloxCre mice. Thus, renal NHE3 is required to maintain blood pressure and steady state plasma sodium levels when dietary sodium chloride intake is modified.

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Short-term nonpressor angiotensin II infusion stimulates sodium transporters in proximal tubule and distal nephron

Cited by 41 publications

References 43 publications

Potassium Supplementation Prevents Sodium Chloride Cotransporter Stimulation During Angiotensin II Hypertension

Potassium Supplementation Prevents Sodium Chloride Cotransporter Stimulation During Angiotensin II Hypertension

Recent Updates on the Proximal Tubule Renin-Angiotensin System in Angiotensin II-Dependent Hypertension

Renal tubular NHE3 is required in the maintenance of water and sodium chloride homeostasis

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