Increased colonic sodium absorption in rats with chronic renal failure is partially mediated by AT1receptor agonism

Abstract

To test the hypothesis that colonic Na+transport is altered in the 5/6 nephrectomized rat model of chronic renal failure (CRF), we measured Na+fluxes across distal colon from control (CON), CRF, and CRF rats treated with the angiotensin II (ANG II) receptor antagonist losartan (+LOS). We also evaluated overall fluid and Na+balance and compared colonic protein and mRNA expression profiles for electroneutral [sodium-hydrogen exchanger (NHE)] and electrogenic Na+transport [epithelial sodium channel (ENaC)] in these groups. Consistent with a 60% enhancement in colonic Na+absorption in CRF, urinary Na+excretion increased by about 50% while serum Na+homeostasis was maintained. These CRF-induced changes in Na+handling were normalized by treatment with LOS. Net Na+absorption was also stimulated in in vitro tissues from CON rats following acute serosal addition of ANG II (10−7M), and this increase was blocked by AT1antagonism but not by an AT2antagonist. In CRF, colonic protein and mRNA expression variably increased for apical NHE2, NHE3, and ENaC α-, β-, γ-subunits, whereas expression of basolateral NHE1 and Na+-K+-ATPase (α-isoform) remained unaltered. Upregulation of the ENaC subunit mRNA was attenuated somewhat by LOS treatment. Previously, we showed that colonic AT1receptor protein is upregulated twofold in CRF, and here we find that AT1and AT2mRNA and AT2protein abundance is unchanged in CRF. We conclude that Na+absorption in CRF rat distal colon is increased due to elevated expression of proteins mediating electroneutral and electrogenic uptake and that it is partially mediated by AT1receptors.