Early polyuria and urinary concentrating defect in potassium deprivation.

Abstract

The time course of the onset of nephrogenic diabetes insipidus and its relationship to aquaporin-2 (AQP2) expression in K(+) deprivation (KD) remains unknown. Rats were fed a K(+)-free diet and killed after 12 h, 1, 2, 3, 6, or 21 days. Serum K(+) concentration was decreased only after, but not before, 3 days of a K(+)-free diet. Urine osmolality, however, decreased as early as 12 h of KD (1,061 +/- 26 vs. 1,487 +/- 102 mosmol/kgH(2)O in control, P < 0.01). It decreased further at 24 h (to 858 +/- 162 mosmol/kgH(2)O in KD, P < 0.004) and remained low at 21 days of KD (436 +/- 58 mosmol/kgH(2)O, P < 0.0001 compared with baseline). Water intake decreased at 12 h (P < 0.002) but increased at 24 h (P < 0.05) and remained elevated at 21 days of KD. Urine volume increased at 24 h of KD (8 +/- 2 to 15 +/- 2 ml/24 h, P < 0.05) and remained elevated at 21 days. Immunoblot analysis demonstrated that AQP2 protein abundance in the outer medulla remained unchanged at 12 h (P > 0.05), decreased at 24 h ( approximately 44%, P < 0.001), and remained suppressed ( approximately 52%, P < 0.03) at 21 days of KD. In the inner medulla the AQP2 protein abundance remained unchanged at both 12 and 24 h of KD. AQP2 protein abundance in the cortex, however, decreased at 12 h ( approximately 47%, P < 0.01) and remained suppressed at 24 h ( approximately 77%, P < 0.001) of KD. Northern blot analysis showed that AQP2 mRNA decreased as early as 12 h of KD in both cortex (P < 0.02) and outer medulla (P < 0.01) and remained suppressed afterward. In conclusion, the urinary concentrating defect in KD is an early event and precedes the onset of hypokalemia. These studies further suggest that the very early urinary concentrating defect in KD (after 12 but before 24 h) results primarily from the suppression of cortical AQP2, whereas the later onset of a urinary concentrating defect (after 24 h) also involves a downregulation of medullary AQP2.

• Authors: H Amlal, C M Krane, Q Chen, M Soleimani
• Journal: American journal of physiology. Renal physiology (Am J Physiol Renal Physiol) Vol. 279 Issue 4 Pg. F655-63 (Oct 2000) ISSN: 1931-857X [Print] United States
• PMID: 10997915 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Aqp2 protein, rat
• Aquaporin 2
• Aquaporin 6
• Aquaporins
• Bicarbonates
• RNA, Messenger
• Water
• Potassium

Topics

• Animals
• Aquaporin 2
• Aquaporin 6
• Aquaporins (genetics, metabolism)
• Bicarbonates (blood)
• Down-Regulation
• Kidney Concentrating Ability (drug effects)
• Kidney Cortex (metabolism)
• Kidney Medulla (metabolism)
• Male
• Osmolar Concentration
• Polyuria (etiology)
• Potassium (administration & dosage, blood, pharmacology)
• RNA, Messenger (metabolism)
• Rats
• Rats, Sprague-Dawley
• Time Factors
• Tissue Distribution
• Urine (chemistry)
• Water (metabolism)