title: Inhibition of angiotensin type 1 receptor impairs renal ability of K conservation in response to K restriction.
abstract: 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 (AT(1)R) 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 AT(1)R. 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 AT(1)R abolished the effect of K restriction on SK channels and tyrosine phosphorylation of ROMK channels. The notion that AT(1)R 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 AT(1)R is involved in mediating the effect of K restriction on superoxide generation, c-Src, and MAPK and that inhibiting AT(1)R impairs renal ability of K conservation in response to K depletion.
authors.affiliation: Department of Medical Genetics, Harbin Medical University, Harbin, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Jin
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Zhi-Jian
authors.initials: ZJ
authors.lastname: Wang
authors.forename: Dao-Hong
authors.initials: DH
authors.lastname: Lin
authors.forename: Wen-Hui
authors.initials: WH
authors.lastname: Wang
mesh_terms: D000804:Angiotensin II / Q000378:metabolism; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D000081247:CSK Tyrosine-Protein Kinase; D005260:Female; D006706:Homeostasis / Q000187:drug effects; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism*; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000502:physiology; D011188:Potassium / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism; D019061:src-Family Kinases
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D044140:Receptor, Angiotensin, Type 1; D013481:Superoxides; D000804:Angiotensin II; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; D020928:Mitogen-Activated Protein Kinases; D019808:Losartan; D011188:Potassium