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Role of angiotensin II and oxidative stress on renal aquaporins expression in hypernatremic rats

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Abstract

The aim of this study was to assess whether endogenous Ang II and oxidative stress produced by acute hypertonic sodium overload may regulate the expression of aquaporin-1 (AQP-1) and aquaporin-2 (AQP-2) in the kidney. Groups of anesthetized male Sprague–Dawley rats were infused with isotonic saline solution (control) or with hypertonic saline solution (Na group, 1 M NaCl), either alone or with losartan (10 mg kg−1) or tempol (0.5 mg min−1 kg−1) during 2 h. Renal function parameters were measured. Groups of unanesthetized animals were injected intraperitoneally with hypertonic saline solution, with or without free access to water intake, Na+W, and Na−W, respectively. The expression of AQP-1, AQP-2, Ang II, eNOS, and NF-kB were evaluated in the kidney by Western blot and immunohistochemistry. AQP-2 distribution was assessed by immunofluorescence. Na group showed increased natriuresis and diuresis, and Ang II and NF-kB expression, but decreased eNOS expression. Losartan or tempol enhanced further the diuresis, and AQP-2 and eNOS expression, as well as decreased Ang II and NF-kB expression. Confocal immunofluorescence imaging revealed labeling of AQP-2 in the apical plasma membrane with less labeling in the intracellular vesicles than the apical membrane in kidney medullary collecting duct principal cells both in C and Na groups. Importantly, our data also show that losartan and tempol induces a predominantly accumulation of AQP-2 in intracellular vesicles. In unanesthetized rats, Na+W group presented increased diuresis, natriuresis, and AQP-2 expression (112 ± 25 vs 64 ± 16; *p < 0.05). Water deprivation increased plasma sodium and diuresis but decreased AQP-2 (46 ± 22 vs 112 ± 25; §p < 0.05) and eNOS expression in the kidney. This study is a novel demonstration that renal endogenous Ang II–oxidative stress, induced in vivo in hypernatremic rats by an acute sodium overload, regulates AQP-2 expression.

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Acknowledgments

This study was supported by grants from the National Scientific and Technical Research Council (CONICET, PIP 1337) and Universidad de Buenos Aires, Argentina (UBACYT B113, 20020100100688, and 20020110200048)

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All authors declare no conflict of interests.

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Correspondence to Silvana L. Della Penna.

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Della Penna, S.L., Cao, G., Kouyoumdzian, N.M. et al. Role of angiotensin II and oxidative stress on renal aquaporins expression in hypernatremic rats. J Physiol Biochem 70, 465–478 (2014). https://doi.org/10.1007/s13105-014-0324-5

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  • DOI: https://doi.org/10.1007/s13105-014-0324-5

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