Local upregulation of colonic angiotensin II receptors enhances potassium excretion in chronic renal failure

The role of angiotensin II (ANG II) in colonic secretion of K(+) was examined in rats with chronic renal failure (CRF). The basal net secretory flux of (86)Rb(+) (as a tracer for K(+)) across the CRF distal colon (-0.20 +/- 0.04 mu eq.cm(-2).h(-1)) was reversed to an absorptive flux (0.35 +/- 0.05 mu eq.cm(-2).h(-1)) by injecting the rats with the AT(1) receptor antagonist, losartan. it similar result was observed when losartan was added to the CRF colonic tissue in vitro. In contrast, an AT(2) receptor antagonist, PD-123319, did not reverse the CRF-induced alterations in Rbi transport across the short-circuited colonic tissue. Plasma concentrations of ANG II, aldosterone, and K(+), as well as the ANG II content of colonic tissues from CRF and normal rats, were similar. However, specific (125)I-labeled ANG II binding sites in rat distal colon increased twofold in CRF [maximal specific binding (B(max)) = 28.6 +/- 1.6 fmol/mg protein] compared with normal (B(max) = 15.2 +/- 0.4 fmol/mg protein). These studies suggest that CRF-induced secretion of K(+) by the colon is mediated by an upregulation of AT(1) receptors present in CRF.