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• W2129393444 abstract "Proximal tubule reabsorption is regulated by systemic and intrinsic mechanisms, including locally produced autocoids. Superoxide, produced by NADPH oxidase enhances NaCl transport in the loop of Henle and the collecting duct, but its role in the proximal tubule is unclear. We measured proximal tubule fluid reabsorption (J v ) in WKY rats and compared that with J v in the spontaneously hypertensive rat (SHR), a model of enhanced renal superoxide generation. Rats were treated with the NADPH oxidase inhibitor apocynin (Apo) or with small interfering RNA for p22 phox , which is the critical subunit of NADPH oxidase. J v was lower in SHR compared with Wistar-Kyoto rats (WKY; WKY: 2.3±0.3 vs SHR: 1.1±0.2 nL/min per millimeter; n=9 to 11; P <0.001). Apo and small interfering RNA to p22 phox normalized J v in SHRs but had no effect in WKY rats. J v was reduced in proximal tubules perfused with S-1611, a highly selective inhibitor of the Na + /H + exchanger 3, the major Na + uptake pathway in the proximal tubule, in WKY rats but not in SHRs. Pretreatment with Apo restored an effect of S-1611 to reduce J v in the SHRs (SHR+Apo: 2.9±0.4 vs SHR+Apo+S-1611: 1.0±0.3 nL/min per millimeter; P <0.001). However, because expression of the Na + /H + exchanger 3 was similar between SHR and WKY rats, this suggests that superoxide affects Na + /H + exchanger 3 activity. Direct microperfusion of Tempol or Apo into the proximal tubule also restored J v in SHRs. In conclusion, superoxide generated by NADPH oxidase inhibits proximal tubule fluid reabsorption in SHRs. This finding implies that proximal tubule fluid reabsorption is regulated by redox balance, which may have profound effects on ion and fluid homeostasis in the hypertensive kidney." @default.
• W2129393444 created "2016-06-24" @default.
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• W2129393444 date "2009-12-01" @default.
• W2129393444 modified "2023-10-15" @default.
• W2129393444 title "Renal Proximal Tubular Reabsorption Is Reduced In Adult Spontaneously Hypertensive Rats" @default.
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• W2129393444 doi "https://doi.org/10.1161/hypertensionaha.109.134783" @default.
• W2129393444 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2783382" @default.
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• W2129393444 hasPublicationYear "2009" @default.
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