AT₁ receptor up-regulation in intestine in chronic renal failure is segment specific

Abstract

 The role of the AT₁ receptor in stimulating colonic K⁺ secretion was investigated in rats with chronic renal failure (CRF) induced by 5/6 nephrectomy. Compared to control rats, CRF rats up-regulate mucosal AT₁ receptors approximately two-fold in the proximal (PC) and distal (DC) colonic segments. In contrast, there was no alteration in AT₁ receptor protein mass in jejunal or ileal mucosa. Using ⁸⁶Rb⁺ as a tracer for transmural K⁺ fluxes, a significant stimulation of the basal K⁺ secretory flux across both PC and DC was observed in vitro and this alteration in K⁺ transport was temporally correlated with the increase in angiotensin II (ANG II) receptors. In both PC and DC the significant increases in the receptor protein were evident 48 h after partial nephrectomy and they were sustained through 6 weeks. These studies support the hypothesis that CRF-induced secretion of K⁺ is mediated by an up-regulation of AT₁ receptors exclusively in the large intestinal segments.