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Am J Physiol Renal Physiol 275: F724-F741, 1998;
0363-6127/98 $5.00
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Vol. 275, Issue 5, F724-F741, November 1998

Reduced AQP1, -2, and -3 levels in kidneys of rats with CRF induced by surgical reduction in renal mass

Tae-Hwan Kwon1, Jørgen Frøkiaer2, Mark A. Knepper3, and Søren Nielsen1

1 Department of Cell Biology, Institute of Anatomy, University of Aarhus, and 2 Department of Clinical Physiology, Aarhus University Hospital and Institute of Experimental Clinical Research, DK-8000 Aarhus, Denmark; and 3 Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892

Urinary concentration characteristically decreases in response to a reduction in renal mass in chronic renal failure (CRF). In the present study, we examined whether there are changes in the expression of aquaporins in rats where CRF was induced by 5/6 nephrectomy. Plasma creatinine levels were significantly elevated consistent with significant CRF: 135.7 ± 15.1 (n = 17, CRF) vs. 33.9 ± 1.1 µmol/l (n = 11, sham), P < 0.05. Two weeks after 5/6 nephrectomy, the remnant kidneys were hypertrophied, and total renal mass increased to 65 ± 3% of sham levels (P < 0.05). Urine production increased markedly from 40 ± 2 to 111 ± 3 µl · min-1 · kg-1 in CRF rats (P < 0.05), whereas urine osmolality and solute-free water reabsorption decreased significantly. Quantitative immunoblotting of total kidney membrane fractions revealed a significant decrease in total kidney AQP2 expression in CRF rats to 43 ± 12% of sham levels (P < 0.05). A similar reduction was observed for AQP1 and AQP3. Furthermore, the increased urine output and decreased urine osmolality persisted in CRF rats despite 7 days treatment with 1-desamino-[8-D-arginine]vasopressin (DDAVP, 0.1 µg/h sc) compared with untreated sham-operated controls. Also, there was no change in AQP2 expression (which remained at 38 ± 3% of sham levels, P < 0.05), urine output, or urine osmolality between CRF rats with or without DDAVP treatment. Immunocytochemistry confirmed the decreased AQP2 expression in collecting duct principal cells in CRF rats, with a predominant apical labeling. In conclusion, the results demonstrated that there was a significant vasopressin-resistant downregulation of AQP2 and AQP3 as well as downregulation of AQP1 associated with the polyuria in CRF rats.

aquaporins; vasopressin; polyuria


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