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This Article Full Text Full Text (PDF) All Versions of this Article: 296/5/F1179    most recent 90725.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Jin, Y. Articles by Wang, W.-H. Search for Related Content PubMed PubMed Citation Articles by Jin, Y. Articles by Wang, W.-H.

Inhibition of angiotensin type 1 receptor impairs renal ability of K conservation in response to K restriction

Departments of ¹Medical Genetics and ²Medical Microbiology, Harbin Medical University, Harbin, China; and ³Department of Pharmacology, New York Medical College, Valhalla, New York

Submitted 4 December 2008 ; accepted in final form 9 February 2009

We have previously demonstrated that ANG II inhibits ROMK-like small-conductance K channels (SK) in the cortical collecting duct from rats on a K-deficient diet (KD) (35). In the present study, we examined the role of angiotensin type 1 receptor (AT₁R) in mediating the effect of K restriction on K secretion. We confirmed the previous finding that K restriction increased the superoxide anion level, c-Src expression, and the phosphorylation of both p38 and extracellular signal-regulated kinase mitogen-activated protein kinase (MAPK) in renal cortex and outer medulla. However, the effect of K restriction on superoxide anion generation, c-Src expression, and MAPK phosphorylation was significantly attenuated in rats receiving losartan, an inhibitor of AT₁R. In contrast, losartan treatment had no effect on superoxide anion level, c-Src expression, and MAPK phosphorylation in animals on a normal K diet (NK). K restriction decreased SK channel activity and increased the tyrosine phosphorylation of ROMK. However, inhibiting AT₁R abolished the effect of K restriction on SK channels and tyrosine phosphorylation of ROMK channels. The notion that AT₁R is involved in regulating renal K excretion was also supported by the experiments with metabolic cages showing that losartan treatment significantly enhanced urinary K loss in rats on a KD diet while it had no effect in animals on a NK diet. Consequently, losartan-treated animals had severe hypokalemia in response to K restriction compared with rats without losartan intake. We conclude that AT₁R is involved in mediating the effect of K restriction on superoxide generation, c-Src, and MAPK and that inhibiting AT₁R impairs renal ability of K conservation in response to K depletion.

angiotensin II; potassium homeostasis; c-Src; mitogen-activated protein kinase; renal potassium secretion