Acute endotoxemia in rats induces down-regulation of V2 vasopressin receptors and aquaporin-2 content in the kidney medulla

Grinevich, Valery; Knepper, Mark A.; Verbalis, Joseph G.; Reyes, Ivan; Aguilera, Greti

doi:10.1111/j.1523-1755.2004.00378.x

Cited by 84 publications

(77 citation statements)

References 45 publications

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“…In contrast to the more severe NaCl-restricted model (16), downregulation of AQP1 and Na-K-ATPase was not observed in the current model, which had no renal impairment. These findings support the importance of ARF in downregulating water channels and ion transporters, as previously reported (6,9,10,15). However, in concert with the earlier conclusion (16), the results of the present in vivo study support the molecular interaction between AVP and ANG II in AQP2, pAQP2, and AQP3 protein expression, as well as AQP2 trafficking in the inner medulla.…”

Section: Discussionsupporting

confidence: 93%

Interaction between vasopressin and angiotensin II in vivo and in vitro: effect on aquaporins and urine concentration

Wang

Summer

et al. 2010

American Journal of Physiology-Renal Physiology

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The study was undertaken to examine the potential cross talk between vasopressin and angiotensin II (ANG II) intracellular signaling pathways. We investigated in vivo and in vitro whether vasopressin-induced water reabsorption could be attenuated by ANG II AT1 receptor blockade (losartan). On a low-sodium diet (0.5 meq/day) dDAVP-treated animals with or without losartan exhibited comparable renal function [creatinine clearance 1.2 Ϯ 0.1 in dDAVPϩlosartan (LSDL) vs. 1.1 Ϯ 0.1 ml·100 g Ϫ1 ·day Ϫ1 in dDAVP alone (LSD), P Ͼ 0.05] and renal blood flow (6.3 Ϯ 0.5 in LSDL vs. 6.8 Ϯ 0.5 ml/min in LSD, P Ͼ 0.05). The urine output, however, was significantly increased in LSDL (2.5 Ϯ 0.2 vs. 1.8 Ϯ 0.2 ml·100 g Ϫ1 ·day Ϫ1 , P Ͻ 0.05) in association with decreased urine osmolality (2,600 Ϯ 83 vs. 3,256 Ϯ 110 mosmol/kgH 2O, P Ͻ 0.001) compared with rats in LSD. Immunoblotting revealed significantly decreased expression of medullary AQP2 (146 Ϯ 6 vs. 176 Ϯ 10% in LSD, P Ͻ 0.01), p-AQP2 (177 Ϯ 13 vs. 214 Ϯ 12% in LSD, P Ͻ 0.05), and AQP3 (134 Ϯ 14 vs. 177 Ϯ 11% in LSD, P Ͻ 0.05) in LSDL compared with LSD. The expressions of AQP1, the ␣ 1-and ␥-subunits of Na-K-ATPase, and the Na-K-2Cl cotransporter were not different among groups. In vitro studies showed that ANG II or dDAVP treatment was associated with increased AQP2 expression and cAMP levels, which were potentiated by cotreatment with ANG II and dDAVP and were inhibited by AT1 blockade. In conclusion, ANG II AT1 receptor blockade in dDAVPtreated rats on a low-salt diet was associated with decreased urine concentration and decreased inner medullary AQP2, p-AQP2, and AQP3 expression, suggesting that AT1 receptor activation plays a significant role in regulating aquaporin expression and modulating urine concentration in vivo. Studies in collecting duct cells were confirmatory.aquaporin; urine concentration; cAMP THERE IS SUBSTANTIAL EVIDENCE that arterial underfilling, either due to decreased cardiac output, e.g., heart failure, or systemic arterial vasodilation, e.g., cirrhosis, is associated with activation of the neurohumoral axis, including the sympathetic nervous system, the renin-angiotensin system, and arginine vasopressin (AVP) (22,23). This neurohumoral response involves compensatory systemic vasoconstriction and renal sodium and water retention to attenuate the arterial underfilling.Much is known about the systemic effects of these components of neurohormonal activation by the use of angiotensinconverting enzyme inhibitors, angiotensin receptor blockers, mineralocorticoid antagonists, and most recently vasopressin receptor antagonists (22,24,25). However, little is known about any potential interaction or cross talk between AVP and angiotensin II (ANG II) at the cellular and molecular level in the kidney.In the collecting duct, AVP binds to the vasopressin V2 receptor on the basolateral membrane of the principal cells, increasing the intracellular levels of cAMP via adenylyl cyclase and thereby activating protein kinase A, which phosphorylates aquaporin-2 (AQP2) with...

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Section: Discussionsupporting

confidence: 93%

Interaction between vasopressin and angiotensin II in vivo and in vitro: effect on aquaporins and urine concentration

Wang

Summer

et al. 2010

American Journal of Physiology-Renal Physiology

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“…Previous studies performed on animals have documented decreased AQP2 expression after intraperitoneal LPS injection as a consequence of down-regulated V 2 receptor activity (35). In addition to the identification of B elements present in the AQP2 promoter, two other findings of the present study provide direct evidence that downregulated AQP2 expression in response to LPS additionally arises from decreased AQP2 gene transcription.…”

Section: Discussionsupporting

confidence: 79%

“…The results of the present study suggest that decreased AQP2 expression after NF-B stimulation participates in the urinary concentration defects observed in tubulo-interstitial inflammatory diseases. This interpretation is supported by observations from animal models showing that endotoxemia induced by intraperitoneal LPS injection or ureteral obstruction were associated with polyuria and decreased levels of AQP2 expression (35,47). Down-regulated levels of AQP2 were additionally observed in animal models of puromycin aminonucleosideand adriamycin-induced nephrotic syndrome (18,20).…”

Section: Discussionmentioning

confidence: 59%

NF-κB Modulates Aquaporin-2 Transcription in Renal Collecting Duct Principal Cells

Hasler

Leroy

Jeon

et al. 2008

Journal of Biological Chemistry

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Renal tubulo-interstitial inflammation is frequently associated with polyuria and urine concentration defects. This led us to investigate the effects of the major pro-inflammatory nuclear factor B (NF-B) pathway on aquaporin 2 (AQP2) expression by the collecting duct. Using immortalized collecting duct principal cells (mpkCCD cl4 ), we found that, acting independently of vasopressin, activation of NF-B by lipopolysaccharide (LPS) decreased AQP2 mRNA and protein levels in a time-and dose-dependent manner but did not decrease AQP2 mRNA stability. Consistently, constitutively active IB kinase ␤ decreased AQP2 expression. The LPSinduced decrease in AQP2 mRNA levels was confirmed in rat kidney slices and was reproduced both under conditions of elevated cAMP concentration and V 2 receptor antagonism. Computer analysis of the AQP2 promoter revealed two putative B elements. Mutation of either B element abolished the LPS-induced decrease of luciferase activity in cells expressing AQP2 promoter-luciferase plasmid constructs. Chromatin immunoprecipitation revealed that LPS challenge decreased p65, increased p50 and p52, and had no effect on RelB and c-Rel binding to B elements of the AQP2 promoter. RNA-mediated interference silencing of p65, p50, and p52 confirmed controlled AQP2 transcription by these NF-B subunits. We additionally found that hypertonicity activated NF-B in mpkCCD cl4 cells, an effect that may counteract the Tonicity-responsive enhancer binding protein (TonEBP)-dependent increase in AQP2 gene transcription. Taken together, these findings indicate that NF-B is an important physiological regulator of AQP2 transcription.Selective transcellular water permeability across the renal epithelium is facilitated by the aquaporin 1 (AQP1) 3 water channel, expressed in the proximal tubule and thin descending limb of Henle's loop (1, 2) and AQP2, -3, and -4, expressed in collecting duct (CD) principal cells (3). AQP2 inserted in the apical plasma membrane enhances CD apical water permeability. Water exits these cells via basolateral AQP3 and AQP4. By controlling both short term (plasma membrane insertion) and long term (transcriptional and post-transcriptional) AQP2 expression, the antidiuretic hormone [8-arginine]vasopressin (AVP) plays a major role in regulating water reabsorption (3-7). In addition to AVP, AQP2 expression is influenced by numerous factors that act independently of AVP including other hormones, i.e. aldosterone and insulin (8, 9), extracellular calcium (10), and environmental tonicity (11-13).The NF-B family of transcription factors consists of five members (p65, p50/p105, p52/p100, RelB, and c-Rel) that contain a Rel-homology domain required for the formation of various combinations of homo-and heterodimers and for DNA binding. Generally, dimers that contain p65 or c-Rel are transcriptional activators, whereas p50 and p52 homodimers act as repressors. The differential dimerization that occurs between NF-B family members allows for cellspecific transcriptional modulation of target genes in response t...

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“…LPS, which potently induces TNF-␣ release, decreases arginine-vasopressin type 2 receptor levels and aquaporin 2 expression in the renal inner medulla (49). In support of this, in a model of sepsis plasma arginine vasopressin did not change but V2 receptor and aquaporin 2 expression were decreased, whereas a siRNA against the TNFR p50 subunit attenuated the decrease in these proteins (58).…”

Section: Na Water Urea and Glucose Transportmentioning

confidence: 82%

Tumor necrosis factor-α: regulation of renal function and blood pressure

Ramseyer

Garvin

2013

American Journal of Physiology-Renal Physiology

149

106

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Acute endotoxemia in rats induces down-regulation of V2 vasopressin receptors and aquaporin-2 content in the kidney medulla

Abstract: The inflammatory response to acute endotoxemia down regulates V2 VP receptors and aquaporin-2 of the kidney inner medulla resulting in prolonged impairment of the renal capacity to concentrate urine.

Cited by 84 publications

References 45 publications

Interaction between vasopressin and angiotensin II in vivo and in vitro: effect on aquaporins and urine concentration

Interaction between vasopressin and angiotensin II in vivo and in vitro: effect on aquaporins and urine concentration

NF-κB Modulates Aquaporin-2 Transcription in Renal Collecting Duct Principal Cells

Tumor necrosis factor-α: regulation of renal function and blood pressure

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