CHANGES IN AQUAPORIN-2 PROTEIN CONTRIBUTE TO THE URINE CONCENTRATING DEFECT IN RATS FED A LOW-PROTEIN DIET

Low-protein diets cause a urinary concentrating defect in rats and hum ans. Previously, we showed that feeding rats a low (8%) protein diet i nduces a change in urea transport in initial inner medullary collectin g ducts (IMCDs) which could contribute to the concentrating defect. No w, we test whether decreased osmotic water permeability (P-f) contribu tes to the concentrating defect by measuring P-f in perfused initial a nd terminal IMCDs from rats fed 18 or 8% protein for 2 wk, In terminal IMCDs, arginine vasopressin (AVP)-stimulated osmotic water permeabili ty was significantly reduced in rats fed 8% protein compared to rats f ed 18% protein, In initial IMCDs, AVP-stimulated osmotic water permeab ility was unaffected by dietary protein, Thus, AVP-stimulated osmotic water permeability is significantly reduced in terminal IMCDs but not in initial IMCDs. Next, we determined if the amount of immunoreactive aquaporin-2 (AQP2, the AVP-regulated water channel) or AQP3 protein wa s altered, Protein was isolated from base or tip regions of rat inner medulla and Western analysis performed using polyclonal antibodies to rat AQP2 or AQP3 (courtesy of Dr, M.A. Knepper, National Institutes of Health, Bethesda, MD), In rats fed 8% protein (compared to rats fed 1 8% protein): (a) AQP2 decreases significantly in both membrane and ves icle fractions from the tip; (b) AQP2 is unchanged in the base; and (c ) AQP3 is unchanged. Together, the results suggest that the decrease i n AVP-stimulated osmotic water permeability results, at least in part, in the decrease in AQP2 protein, We conclude that water reabsorption, like urea reabsorption, responds to dietary protein restriction in a manner that would limit urine concentrating capacity.