SAT-119 Mechanisms of (Pro)renin Receptor Expression in the Kidney of Dahl Salt-Sensitive Rats by High Salt Intake

We recently reported that high salt (HS) intake increased the (pro)renin receptor ((P)RR) expression by 3-5 fold in several nephron segments of Sprague-Dawley rats (Peptides 63: 156-162, 2015). The preset study examined the effects of HS intake on the renal (P)RR expression in Dahl-Salt sensitive (DS) rats. Male DS rats were fed a normal salt (NS) diet (0.6%NaCl) and a HS diet (8%NaCl) for 4weeks. A part of the rats fed the HS diet were treated orally with angiotensin II type 1 receptor (AT 1 R) antagonist, candesartan (Can,3mg/kg/day) or mineralocorticoid receptor (MR) antagonist, spironolactone (Spi, 100mg/kg/day). The (P)RR expression in nephron segments was examined by immunoblot and immunohistochemical analyses. HS intake increased the blood pressure, which did not significantly affected by Can or Spi. (P)RR was expressed in the all kidney sections, glomeruli, proximal tubules (PT), medullary thick ascending limbs and inner medullary collecting ducts. HS intake increased the (P)RR expression in the cortex by 22.6 fold (p<0.001) and the PT by 4.9 fold (p<0.01), but did not change it in the other sections or segments. Can inhibited the HS intake-increased (P)RR expression in the cortex by 32% (p<0.05), Spi inhibited it by 89% (p<0.001), but neither drug did not inhibit the HS intake-increased (P)RR expression in the PT. Immunohistochemical analysis also revealed that HS intake increased the (P)RR expression in the PT and distal tubules, and that Can and Spi inhibited the HS intake-increased (P)RR expression in the distal tubules. Additionally, deoxycorticosterone acetate (DOCA, 50mg/kg/week) administered to rats fed the NS diet for 4 weeks increased the (P)RR expression in the cortex by 80% (p<0.001) and distal tubules, but not in the PT. These results indicate that HS intake-increased (P)RR expression is enhanced in the PT and distal tubules of DS rats. The mechanisms of HS intake-increased (P)RR expression may be AT 1 R and MR-dependent manner in the distal tubules, but AT 1 R or MR-independent manner in the PT.

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Salt loading enhances rat renal TxA2/PGH2 receptor expression and TGF response to U-46,619

AJP Renal Physiology ◽

10.1152/ajprenal.1997.273.6.f976 ◽

1997 ◽

Vol 273 (6) ◽

pp. F976-F983 ◽

Cited By ~ 11

Author(s):

William J. Welch ◽

Bo Peng ◽

Kazuhisa Takeuchi ◽

Keishi Abe ◽

Christopher S. Wilcox

Keyword(s):

Salt Intake ◽

Receptor Activation ◽

High Salt ◽

Receptor Expression ◽

Tubuloglomerular Feedback ◽

Kidney Cortex ◽

Salt Loading ◽

Receptor Mrna ◽

High Salt Intake ◽

Low Salt

The tubuloglomerular feedback (TGF) response is potentiated by thromboxane A2(TxA2) and/or prostaglandin endoperoxide (PGH2) acting on specific receptors. Infusion of the TxA2/PGH2mimetic, U-46,619, into conscious rats leads to hypertension that is potentiated by a high-salt intake. Therefore, we tested the hypothesis that a high-salt intake enhances the expression of transcripts for TxA2/PGH2receptors in the kidney and glomeruli and enhances the response of TGF to TxA2/PGH2receptor stimulation. Groups of rats were accommodated to a low-salt (LS), normal salt (NS), or high-salt (HS) diet for 8–10 days. TxA2/PGH2receptor mRNA was detected by reverse transcription-polymerase chain reaction in kidney cortex, isolated glomeruli, and abdominal aorta. TxA2/PGH2mRNA abundance was significantly ( P< 0.001) increased during intake of high-salt compared with low-salt diets in the kidney cortex (1.34 ± 0.10 vs. 0.84 ± 0.04 arbitrary units) and isolated outer cortical glomeruli (0.68 ± 0.04 vs. 0.32 ± 0.03 arbitrary units), but there was no effect of salt on TxA2/PGH2receptor mRNA expression in the aorta. Maximal TGF responses were assessed from the increase in proximal stop flow pressure (an index of glomerular capillary pressure) during increases in loop of Henle perfusion with artificial tubular fluid from 0 to 40 nl/min. Compared with vehicle, the enhancement of maximal TGF with U-46,619 (10−6 M) added to the perfusate was greater in rats adapted to high-salt than normal salt (HS: +9.6 ± 1.1 vs. NS: +5.1 ± 0.4 mmHg; P < 0.001) or low-salt (LS: +3.8 ± 1.3 mmHg; P < 0.001) intakes. Responses to U-46,619 at each level of salt intake were blocked by >70% by the TxA2/PGH2receptor antagonist ifetroban. In contrast, enhancement of TGF by peritubular capillary perfusion of arginine vasopressin (AVP; 10−7 M) was similar in high-salt and low-salt rats (HS: +1.5 ± 0.6 vs. LS: +1.6 ± 0.5 mmHg; not significant). We conclude that salt loading increases selectively the abundance of TxA2/PGH2receptor transcripts in the kidney cortex and glomerulus, relative to the aorta, and enhances selectively TGF responses to TxA2/PGH2receptor activation but not to AVP.

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High Salt Intake–Increased (Pro)renin Receptor Expression Is Exaggerated in the Kidney of Dahl Salt-Sensitive Rats

Hypertension ◽

10.1161/hypertensionaha.119.13905 ◽

2020 ◽

Vol 75 (6) ◽

pp. 1447-1454

Author(s):

Seiko Yamakoshi ◽

Osamu Ito ◽

Rong Rong ◽

Yusuke Ohsaki ◽

Takahiro Nakamura ◽

...

Keyword(s):

Renal Cortex ◽

Salt Intake ◽

High Salt ◽

Proximal Tubules ◽

Receptor Expression ◽

Dependent Manner ◽

Mineralocorticoid Receptor Antagonist ◽

Salt Diet ◽

High Salt Intake ◽

Distal Tubules

The (P)RR ([pro]renin receptor) was identified as a new component of the renin-angiotensin system. We previously reported that high salt (HS) intake increased the (P)RR expression in several nephron segments of Sprague-Dawley rats. Other studies reported HS intake increased the XO (xanthine oxidase) activity and an MR (mineralocorticoid receptor) antagonist inhibited HS intake–increased (P)RR expression in the kidneys of Dahl salt-sensitive (DS) rats. The present study examined the effects of HS intake on (P)RR expression in the kidney of DS rats. Male DS rats were fed a normal salt diet or an HS diet for 4 weeks. Some of the rats fed on the HS diet were treated with the XO inhibitor, febuxostat, and the MR antagonist, spironolactone. Immunoblot and immunohistochemical analyses showed that HS intake increased (P)RR expression in the renal cortex by 22.6-fold, the proximal tubules by 4.9-fold and the distal tubules, respectively. Both febuxostat and spironolactone inhibited HS intake–increased (P)RR expression in the renal cortex. Febuxostat inhibited HS intake–increased (P)RR expression in the proximal tubules, whereas spironolactone inhibited HS intake–increased (P)RR expression in the distal tubules. Additionally, deoxycorticosterone acetate increased (P)RR expression in the renal cortex and distal tubules but not in the proximal tubules of DS rats fed the normal salt diet. These results indicate that HS intake greatly increases (P)RR expression in the renal cortex of DS rats. The mechanisms of HS intake–increased (P)RR expression may work in an XO-dependent manner in the proximal tubules and an MR-dependent manner in the distal tubules.

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A2298 Regulatory Mechanisms of (Pro)renin Receptor Expression in the Kidney of Dahl Salt-Sensitive Rats by High Salt Intake

Journal of Hypertension ◽

10.1097/01.hjh.0000548068.65919.6a ◽

2018 ◽

Vol 36 ◽

pp. e20-e21

Author(s):

Seiko Yamakoshi ◽

Osamu Ito ◽

Rong Rong ◽

Yusuke Ohsaki ◽

Takahiro Nakamura ◽

...

Keyword(s):

Salt Intake ◽

High Salt ◽

Receptor Expression ◽

Regulatory Mechanisms ◽

High Salt Intake

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High Salt Intake and Stroke: Meta-analysis of the Epidemiologic Evidence

CNS Neuroscience & Therapeutics ◽

10.1111/j.1755-5949.2012.00355.x ◽

2012 ◽

Vol 18 (8) ◽

pp. 691-701 ◽

Cited By ~ 35

Author(s):

Xiu-Yang Li ◽

Xian-Lei Cai ◽

Ping-Da Bian ◽

Liu-Ru Hu

Keyword(s):

Salt Intake ◽

Meta Analysis ◽

High Salt ◽

Epidemiologic Evidence ◽

High Salt Intake

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High Salt Intake Delayed Angiotensin II-Induced Hypertension in Mice With a Genetic Variant of NADPH Oxidase

American Journal of Hypertension ◽

10.1038/ajh.2010.173 ◽

2011 ◽

Vol 24 (1) ◽

pp. 114-118 ◽

Cited By ~ 18

Author(s):

M. Z. Haque ◽

D. S. A. Majid

Keyword(s):

Angiotensin Ii ◽

Nadph Oxidase ◽

Genetic Variant ◽

Salt Intake ◽

High Salt ◽

High Salt Intake ◽

Induced Hypertension

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Hypoxia-Inducible Factor Prolyl-Hydroxylase 2 Senses High-Salt Intake to Increase Hypoxia Inducible Factor 1α Levels in the Renal Medulla

Hypertension ◽

10.1161/hypertensionaha.109.145896 ◽

2010 ◽

Vol 55 (5) ◽

pp. 1129-1136 ◽

Cited By ~ 30

Author(s):

Zhengchao Wang ◽

Qing Zhu ◽

Min Xia ◽

Pin-Lan Li ◽

Shante J. Hinton ◽

...

Keyword(s):

Salt Intake ◽

Hypoxia Inducible Factor ◽

Renal Medulla ◽

Prolyl Hydroxylase ◽

High Salt ◽

Hypoxia Inducible Factor 1Α ◽

High Salt Intake

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Differential responses to salt supplementation in adult male and female rat adrenal glands following intrauterine growth restriction

Journal of Endocrinology ◽

10.1530/joe-10-0421 ◽

2011 ◽

Vol 209 (1) ◽

pp. 85-94 ◽

Cited By ~ 3

Author(s):

Karine Bibeau ◽

Mélissa Otis ◽

Jean St-Louis ◽

Nicole Gallo-Payet ◽

Michèle Brochu

Keyword(s):

Protein Expression ◽

Adrenal Glands ◽

Salt Intake ◽

High Salt ◽

Receptor Subtypes ◽

Mrna Levels ◽

Female Rat ◽

Angiotensin Ii Receptor ◽

Intrauterine Growth ◽

High Salt Intake

In low sodium-induced intrauterine growth restricted (IUGR) rat, foetal adrenal steroidogenesis as well as the adult renin–angiotensin–aldosterone system (RAAS) is altered. The aim of the present study was to determine the expression of cytochrome P450 aldosterone synthase (P450aldo) and of angiotensin II receptor subtypes 1 (AT1R) and 2 (AT2R) in adult adrenal glands and whether this expression could be influenced by IUGR and by high-salt intake in a sex-specific manner. After 6 weeks of 0.9% NaCl supplementation, plasma renin activity, P450aldo expression and serum aldosterone levels were decreased in all groups. In males, IUGR induced an increase in AT1R, AT2R, and P450aldo levels, without changes in morphological appearance of the zona glomerulosa (ZG). By contrast, in females, IUGR had no effect on the expression of AT1R, but increased AT2R mRNA while decreasing protein expression of AT2R and P450aldo. In males, salt intake in IUGR rats reduced both AT1R mRNA and protein, while for AT2R, mRNA levels decreased whereas protein expression increased. In females, salt intake reduced ZG size in IUGR but had no affect on AT1R or AT2R expression in either group. These results indicate that, in response to IUGR and subsequently to salt intake, P450aldo, AT1R, and AT2R levels are differentially expressed in males and females. However, despite these adrenal changes, adult IUGR rats display adequate physiological and adrenal responses to high-salt intake, via RAAS inhibition, thus suggesting that extra-adrenal factors likely compensate for ZG alterations induced by IUGR.

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