Long term vasopressin regulation of renal AQPs and urea transporters in mice with a reduced urinary concentrating ability

Abstract

AQP1 null mice (AQP1 KO) fail to generate a hypertonic medullary interstitium and have a urinary concentrating defect. This study used AQP1 KO mice to investigate how long term vasopressin (AVP) regulates renal aquaporins (AQP) and urea transporters (UTA) in the absence of high osmotic stress. In AQP1 KO mice 6 days of AVP infusion slightly increased urine osmolality (856 ± 33 mOsm vs 752 ± 20 mOsm, P≤0.05). AVP decreased AQP3 mRNA (0.70 ± 0.07 vs 1.00 ± 0.10, P≤0.05) in the inner medulla and did not change AQP3 protein in either the cortex or inner medulla. AVP did not change AQP2 mRNA expression, but increased AQP2 protein (187 ± 12.5 vs 100 ± 9.1%, P≤0.05) in the inner medulla. In the cortex AQP2 mRNA and protein increased (mRNA: 1.68 ± 0.14 vs 1.00 ± 0.07; protein: 143 ± 13.9 vs 100 ± 6.6%, P≤0.05). AVP increased UTA1 mRNA and protein in the inner medulla (mRNA: 2.09 ± 0.1 vs 1.00 ± 0.22; protein: 184 ± 30.0% vs 100 ± 18.1%, P≤0.05). AVP increased collagen 1α1 chain mRNA in the inner medulla and cortex (1.78 ± 0.23 vs 1.00 ± 0.16; 1.66 ± 0.21 vs 1.00 ± 0.24, respectively, P≤0.05) and collagen III mRNA in the cortex (1.87 ± 0.21 vs 1.00 ± 0.23, P≤0.05). The increases in collagen expression did not occur in AVP‐infused wild type mice. We conclude that reduced osmolality in the renal medulla of APQ1 KO mice affects long term AVP‐induced AQP3 and collagens I and III mRNA and AQP 3 protein expression, but does not affect AQP2 and UTA1 protein expression.