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 86Rb+ (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 AT1 receptor antagonist, losartan. A similar result was observed when losartan was added to the CRF colonic tissue in vitro. In contrast, an AT2 receptor antagonist, PD-123319, did not reverse the CRF-induced alterations in Rb+ 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 125I-labeled ANG II binding sites in rat distal colon increased twofold in CRF [maximal specific binding (Bmax) = 28.6 +/- 1.6 fmol/mg protein] compared with normal (Bmax = 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 AT1 receptors present in CRF.
Hatch
M
M
Department of Medicine, University of California at Irvine 92697, USA.
Freel
R W
RW
Vaziri
N D
ND
D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000097:blood / Q000378:metabolism; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D003106:Colon / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D019808:Losartan / Q000494:pharmacology; D008297:Male; D011188:Potassium / Q000097:blood / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000378:metabolism*; D012414:Rubidium Radioisotopes / Q000378:metabolism; D015854:Up-Regulation
D057911:Angiotensin Receptor Antagonists; D007093:Imidazoles; D011725:Pyridines; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D012414:Rubidium Radioisotopes; D000804:Angiotensin II; C073402:PD 123319; D000450:Aldosterone; D019808:Losartan; D011188:Potassium