Angiotensin II involvement in adaptive enteric oxalate excretion in rats with chronic renal failure induced by hyperoxaluria.
Enteric secretion of oxalate is induced in rats that have chronic renal failure produced by 5/6 nephrectomy. The purpose of the present study was to examine renal and intestinal handling of oxalate in rats with chronic renal failure (CRF) induced by chronic hyperoxaluria. A rat model for chronic renal failure, induced by chronic hyperoxaluria (CH-CRF), was produced by unilateral nephrectomy combined with dietary ethylene glycol for 4 weeks. Both intact and unilateral nephrectomized rats (UN) without the oxalate load served as controls. Renal handling of oxalate was assessed by measurement of renal clearance of oxalate and creatinine while colonic handling of oxalate and chloride was determined by in vitro transepithelial flux measurements. Angiotensin II mediation was assessed by sensitivity of the transport processes to the AT(1) receptor antagonist losartan. Renal and colonic handling of oxalate in UN rats were similar to intact controls. The CH-CRF rats were hyperoxalemic, hyperoxaluric, and exhibited a twofold increase in oxalate clearance despite a 50% drop in creatinine clearance. Distal (but not proximal) colonic handling of oxalate in CH-CRF rats was reversed from net oxalate absorption seen in UN and intact controls to net secretion that was sensitive to losartan in vitro.


CONCLUSIONS
Although enteric oxalate secretion can be correlated with elevations in plasma oxalate in the absence of overt renal insufficiency by an ANG II-independent mechanism, the present results suggest that some degree of renal insufficiency is necessary to induce ANG II-mediated colonic oxalate secretion.
Hatch
Marguerite
M
Department of Pathology, Immunology & Laboratory Medicine, College of Medicine, University of Florida, 1600 SW Archer Road, PO Box 100275, Gainesville, FL 32610, USA. hatchma@ufl.edu
Freel
Robert W
RW
D000222:Adaptation, Physiological; D000804:Angiotensin II / Q000378:metabolism*; D047228:Angiotensin II Type 1 Receptor Blockers; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002712:Chlorides / Q000378:metabolism; D003106:Colon / Q000378:metabolism*; D003404:Creatinine / Q000652:urine; D006959:Hyperoxaluria / Q000150:complications*; D007408:Intestinal Absorption; D007668:Kidney / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000209:etiology* / Q000378:metabolism*; D019808:Losartan / Q000494:pharmacology; D008297:Male; D009994:Osmolar Concentration; D010070:Oxalates / Q000378:metabolism* / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley
D047228:Angiotensin II Type 1 Receptor Blockers; D002712:Chlorides; D010070:Oxalates; D000804:Angiotensin II; D003404:Creatinine; D019808:Losartan