Upregulation of aquaporin 2 water channel expression in pregnant rats

• Published in: The Journal of clinical investigation 1998-03, Vol.101 (5), p.1076-1083
• Main Authors: Ohara, M, Martin, P Y, Xu, D L, St John, J, Pattison, T A, Kim, J K, Schrier, R W
• Format: Article
• Language: English
• Subjects: Actins - metabolism; Animals; Aquaporin 2; Aquaporin 6; Aquaporins; Arginine Vasopressin - metabolism; Benzazepines - pharmacology; Blotting, Northern; Blotting, Western; Female; Fluorescent Antibody Technique, Indirect; Gene Expression; Immunohistochemistry; Ion Channels - immunology; Ion Channels - metabolism; Kidney - metabolism; Osmolar Concentration; Pregnancy; Pregnancy, Animal - blood; Pregnancy, Animal - metabolism; Pregnancy, Animal - urine; Rats; Rats, Sprague-Dawley; RNA, Messenger - metabolism; Sodium - metabolism; Up-Regulation; Vasopressins - metabolism; Water - metabolism
• ISSN: 0021-9738
• DOI: 10.1172/jci649

Water retention is characteristic of pregnancy but the mechanism(s) of the altered water metabolism has yet to be elucidated. The collecting duct water channel, aquaporin 2 (AQP2), plays a pivotal role in the renal water regulation, and we hypothesized that AQP2 expression could be modified during pregnancy. Sprague-Dawley female rats were studied on days 7 (P7), 14 (P14), and 20 (P20) of pregnancy, and expression of AQP2 in papillae was examined. Nonpregnant (NP) littermates were used as controls. Plasma osmolalities were significantly lower in pregnant rats by day 7 of gestation (P7 283.8+/-1.82, P14 284.3+/-1.64, P < 0.001, P20 282. 4+/-1.32, P < 0.0001, vs. NP 291.8+/-1.06 mosmol/kgH2O). However, plasma vasopressin concentrations in pregnant rats were not significantly different than in nonpregnant rats (NP 1.03+/-0.14, P7 1.11+/-0.21, P14 1.15+/-0.21, P20 1.36+/-0.24 pg/ml, NS). The mRNA of AQP2 was increased early during pregnancy: AQP2/beta actin: P7 196+/-17.9, P14 200+/-6.8, and P20 208+/-15.5%, P < 0.005 vs. NP (100+/-11.1%). AQP2 protein was also increased during pregnancy: AQP2 protein: P7 269+/-10.0, P14 251+/-12.0, P < 0.0001, and P20 250+/-13.6%, P < 0.001 vs. NP (100+/-12.5%). The effect of V2 vasopressin receptor antagonist, OPC-31260, was then investigated. AQP2 mRNA was suppressed significantly by OPC-31260 administration to P14 rats (AQP2/beta actin: P14 with OPC-31260 39.6+/-1.7%, P < 0.001 vs. P14 with vehicle) and was decreased to the same level of expression as NP rats receiving OPC-31260. Similar findings were found with the analysis of AQP2 protein. The decreased plasma osmolality of P14 rats was not modified by OPC-31260. The results of the study indicate that upregulation of AQP2 contributes to the water retention in pregnancy through a V2 receptor-mediated effect. In addition to vasopressin, other factors may be involved in this upregulation.