We have previously demonstrated that angiotensin II (AngII) inhibits ROMK-like small conductance K channels (SK) in the CCD from rats on a K-deficient diet (KD) (31). In the present study, we examined the role of 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 ERK mitogen activated protein kinase (MAPK) in renal cortex and outer medulla (OM). 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 in comparison to 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.