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

Wang, Weidong; Li, Chunling; Summer, Sandra N.; Falk, Sandor; Schrier, Robert W.

doi:10.1152/ajprenal.00168.2010

Cited by 33 publications

(22 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, studies have demonstrated that ANG II stimulates V2R expression in inner medullary collecting ducts (51). Vasopressin-modulated AQP2 trafficking and expression can be enhanced by ANG II (27,32), and vasopressin, together with ANG II, determines urinary concentration via coregulation with collecting duct water channels (26,48). The present findings indeed showed a paradoxical, opposite effect of ANG II on the water transport properties of obstructed kidneys.…”

Section: Discussionsupporting

confidence: 63%

Aliskiren restores renal AQP2 expression during unilateral ureteral obstruction by inhibiting the inflammasome

Wang

Luo

Lin

et al. 2015

American Journal of Physiology-Renal Physiology

Self Cite

View full text Add to dashboard Cite

Ureteral obstruction is associated with reduced expression of renal aquaporins (AQPs), urinary concentrating defects, and an enhanced inflammatory response, in which the renin-angiotensin system (RAS) may play an important role. We evaluated whether RAS blockade by a direct renin inhibitor, aliskiren, would prevent the decreased renal protein expression of AQPs in a unilateral ureteral obstruction (UUO) model and what potential mechanisms may be involved. UUO was performed for 3 days (3UUO) and 7 days (7UUO) in C57BL/6 mice with or without aliskiren injection. In 3UUO and 7UUO mice, aliskiren abolished the reduction of AQP2 protein expression but not AQP1, AQP3, and AQP4. mRNA levels of renal AQP2 and vasopressin type 2 receptor were decreased in obstructed kidneys of 7UUO mice, which were prevented by aliskiren treatment. Aliskiren treatment was also associated with a reduced inflammatory response in obstructed kidneys of UUO mice. Aliskiren significantly decreased mRNA levels of several proinflammatory factors, such as transforming growth factor-β and tumor necrosis factor-α, seen in obstructed kidneys of UUO mice. Interestingly, mRNA and protein levels of the NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome components apoptosis-associated speck-like protein containing a caspase recruitment domain, caspase-1, and IL-1β were dramatically increased in obstructed kidneys of 7UUO mice, which were significantly suppressed by aliskiren. In primary cultured inner medullary collecting duct cells, IL-1β significantly decreased AQP2 expression. In conclusions, RAS blockade with the direct renin inhibitor aliskiren increased water channel AQP2 expression in obstructed kidneys of UUO mice, at least partially by preventing NLRP3 inflammasome activation in association with ureteral obstruction.

show abstract

Section: Discussionsupporting

confidence: 63%

Aliskiren restores renal AQP2 expression during unilateral ureteral obstruction by inhibiting the inflammasome

Wang

Luo

Lin

et al. 2015

American Journal of Physiology-Renal Physiology

Self Cite

View full text Add to dashboard Cite

show abstract

“…5,6 Furthermore, pharmacologic blockade of AT 1 receptors with losartan attenuates maximal urine osmolality in normal mice, suggesting that physiologic actions of AT 1 receptors modulate water handling. 5,31 Our previous studies using mice lacking only the AT 1A receptor isoform have suggested that their urinary concentrating defect is due to renal resistance to vasopressin because we found normal plasma vasopressin levels at baseline that increase with thirsting and blunted response to exogenous dDAVP. However, AT 1A receptor-deficient mice also have marked hypotension, impaired renal sodium handling, and reduced expression of key sodium transporters in the kidney, all of which may have effects on water handling that are independent of alterations in water permeability of the collecting duct.…”

Section: Discussionmentioning

confidence: 67%

AT1 Receptors in the Collecting Duct Directly Modulate the Concentration of Urine

Stegbauer

Gurley

Sparks

et al. 2011

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

Mice lacking AT 1 angiotensin receptors have an impaired capacity to concentrate the urine, but the underlying mechanism is unknown. To determine whether direct actions of AT 1 receptors in epithelial cells of the collecting duct regulate water reabsorption, we used Cre-Loxp technology to specifically eliminate AT 1A receptors from the collecting duct in mice (CD-KOs). Although levels of AT 1A receptor mRNA in the inner medulla of CD-KO mice were significantly reduced, their kidneys appeared structurally normal. Under basal conditions, plasma and urine osmolalities and urine volumes were similar between CD-KO mice and controls. The increase in urine osmolality in response to water deprivation or vasopressin administration, however, was consistently attenuated in CD-KO mice. Similarly, levels of aquaporin-2 protein in inner and outer medulla after water deprivation were significantly lower in CD-KO mice compared with controls, despite its normal localization to the apical membrane. In summary, these results demonstrate that AT 1A receptors in epithelial cells of the collecting duct directly modulate aquaporin-2 levels and contribute to the concentration of urine. The renin-angiotensin system (RAS) has myriad physiologic actions including the regulation of water homeostasis through modulation of thirst, vasopressin release, and urinary concentrating mechanisms. 1-5 Pharmacologic and gene targeting studies suggest that these actions are mediated primarily by type 1 (AT 1 ) receptors. 5,6 Mice have two AT 1 receptor isoforms, AT 1A and AT 1B , which are highly homologous. The AT 1A receptor is predominantly expressed in most tissues including the kidney and is the murine homologue to the single human AT 1 receptor. Mice completely lacking AT 1A receptors develop polyuria and an impaired urinary concentrating capacity, with an attenuated increase in urine osmolality after water deprivation or vasopressin administration. 5,6 On the other hand, gene targeting studies have demonstrated distinct roles for the AT 1B receptor in the regulation of thirst. 7,8 Nonetheless, the precise mechanisms and cellular targets of AT 1A receptors responsible for regulating urine concentration have not been precisely documented.Evidence from in vivo and in vitro studies suggests that the collecting duct is an important target for the modulation of water handling by the RAS. For example, in cell culture experiments, it

show abstract

“…Water reabsorption by the luminal AQP2 water channel in the collecting duct is a major factor in water homeostasis and urinary concentration. The subcellular localization and activity of this channel is regulated on the molecular level by phosphorylation of several residues including serines 256 and 261 [31][32][33][34] integrating various signals including stimulation by vasopressin or angiotensin II [45]. Our results indicate that AQP2 is stimulated as indicated by increased phosphorylation of Ser256 and by enhanced staining at the luminal membrane in animals receiving NH 4 Cl in water.…”

Section: Induction Of Acidosis In Rodentsmentioning

confidence: 62%

Induction of Metabolic Acidosis with Ammonium Chloride (NH<sub>4</sub>Cl) in Mice and Rats – Species Differences and Technical Considerations

Nowik

Kampik

Mihailova

et al. 2010

Cell Physiol Biochem

View full text Add to dashboard Cite

Ammonium chloride addition to drinking water is often used to induce metabolic acidosis (MA) in rodents but may also cause mild dehydration. Previous microarray screening of acidotic mouse kidneys showed upregulation of genes involved in renal water handling. Thus, we compared two protocols to induce metabolic acidosis in mice and rats: standard 0.28M NH 4 Cl in drinking water or an equivalent amount of NH 4 Cl in food. Both treatments induced MA in mice and rats. In rats, NH 4 Cl in water caused signs of dehydration, reduced mRNA abundance of the vasopression receptor 2 (V2R), increased protein abundance of the aquaporin water channels AQP2 and AQP3 and stimulated phosphorylation of AQP2 at residues Ser256 and Ser261. In contrast, NH 4 Cl in food induced massive diuresis, decreased mRNA levels of V2R, AQP2, and AQP3, did not affect protein abundance of AQP2 and AQP3, and stimulated phosphorylation at Ser261 but not pSer256 of AQP2. In mice, NH 4 Cl in drinking water stimulated urine concentration, increased AQP2 and V2R mRNA levels, and enhanced AQP2 and AQP3 protein expression with higher levels of AQP2 pSer256 and pSer261. Addition of NH 4 Cl to food, stimulated diuresis, had no effect on mRNA levels of AQP2, AQP3, and V2R, and enhanced only AQP3 protein abundance whereas pSer256-AQP2 and pSer261-AQP2 remained unaltered. Similarly, AQP2 staining was more intense and luminal in kidney from mice with NH 4 Cl in water but not in food. Pendrin, SNAT3 and PEPCK mRNA expression in mouse kidney were not affected by the route of NH 4 Cl application. Thus, addition of NH 4 Cl to water or food causes MA but has differential effects on diuresis and expression of mRNAs and proteins related to renal water handling. Moreover, mice and rats respond differently to NH 4 Cl loading, and increased water intake and diuresis may be a compensatory mechanism during MA. It may be necessary to consider these effects in planning and interpreting experiments of NH 4 Cl supplementation to animals. 1060

show abstract

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

Cited by 33 publications

References 30 publications

Aliskiren restores renal AQP2 expression during unilateral ureteral obstruction by inhibiting the inflammasome

Aliskiren restores renal AQP2 expression during unilateral ureteral obstruction by inhibiting the inflammasome

AT1 Receptors in the Collecting Duct Directly Modulate the Concentration of Urine

Induction of Metabolic Acidosis with Ammonium Chloride (NH<sub>4</sub>Cl) in Mice and Rats – Species Differences and Technical Considerations

Contact Info

Product

Resources

About