title: Upregulation of aquaporin 2 water channel expression in pregnant rats.
abstract: 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.
authors.affiliation: Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.
authors.forename: M
authors.initials: M
authors.lastname: Ohara
authors.forename: P Y
authors.initials: PY
authors.lastname: Martin
authors.forename: D L
authors.initials: DL
authors.lastname: Xu
authors.forename: J
authors.initials: J
authors.lastname: St John
authors.forename: T A
authors.initials: TA
authors.lastname: Pattison
authors.forename: J K
authors.initials: JK
authors.lastname: Kim
authors.forename: R W
authors.initials: RW
authors.lastname: Schrier
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D051399:Aquaporin 2; D051403:Aquaporin 6; D020346:Aquaporins; D001127:Arginine Vasopressin / Q000378:metabolism; D001552:Benzazepines / Q000494:pharmacology; D015152:Blotting, Northern; D015153:Blotting, Western; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D015870:Gene Expression; D007150:Immunohistochemistry; D007473:Ion Channels / Q000276:immunology / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D009994:Osmolar Concentration; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000097:blood / Q000378:metabolism* / Q000652:urine; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism; D015854:Up-Regulation; D014667:Vasopressins / Q000378:metabolism; D014867:Water / Q000378:metabolism
chemical_list: D000199:Actins; C496025:Aqp2 protein, rat; D051399:Aquaporin 2; D051403:Aquaporin 6; D020346:Aquaporins; D001552:Benzazepines; D007473:Ion Channels; D012333:RNA, Messenger; D014867:Water; D014667:Vasopressins; D001127:Arginine Vasopressin; C076251:mozavaptan; D012964:Sodium