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• W2168032910 abstract "Oxidative stress modulates angiotensin (Ang) II type 1 receptor (AT(1)R) expression and function. Ang II activates renal Na(+)/H(+) exchanger 3 (NHE3) to increase sodium reabsorption, but the mechanisms are still elusive. In addition, the upregulation of AT(1)R during oxidative stress could promote sodium retention and lead to an increase in blood pressure. Herein, we investigated the mechanism of Ang II-mediated, AT(1)R-dependent renal NHE3 regulation and effect of oxidative stress on AT(1)R signaling and development of hypertension. Male Sprague-Dawley rats received tap water (control) or 30 mmol/L of l-buthionine-sulfoximine, an oxidant, with and without 1 mmol/L of Tempol, an antioxidant, for 3 weeks. l-Buthionine-sulfoximine-treated rats exhibited oxidative stress and high blood pressure. Incubation of renal proximal tubules with Ang II caused significantly higher NHE3 activation in l-buthionine-sulfoximine-treated rats compared with control. The activation of NHE3 was sensitive to AT(1)R blocker and inhibitors of phospholipase C, tyrosine kinase, janus kinase 2 (Jak2), Ca(2+)-dependent calmodulin (CaM), and Ca(2+) chelator. Also, incubation of proximal tubules with Ang II caused Jak2-dependent CaM phosphorylation, which led to Jak2-CaM complex formation and increased Jak2-CaM interaction with NHE3. The activation of these signaling molecules was exaggerated in l-buthionine-sulfoximine-treated rats, whereas Tempol normalized the AT(1)R signaling. In conclusion, Ang II activates renal proximal tubular NHE3 through novel pathways that involve phospholipase C and an increase in intracellular Ca(2+), Jak2, and CaM. In addition, oxidative stress exaggerates Ang II signaling, which leads to overstimulation of renal NHE3 and contributes to an increase in blood pressure." @default.
• W2168032910 created "2016-06-24" @default.
• W2168032910 creator A5021765152 @default.
• W2168032910 creator A5085220617 @default.
• W2168032910 date "2011-03-01" @default.
• W2168032910 modified "2023-09-23" @default.
• W2168032910 title "Oxidative Stress Causes Renal Angiotensin II Type 1 Receptor Upregulation, Na + /H + Exchanger 3 Overstimulation, and Hypertension" @default.
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• W2168032910 doi "https://doi.org/10.1161/hypertensionaha.110.162339" @default.
• W2168032910 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/21282559" @default.
• W2168032910 hasPublicationYear "2011" @default.
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