Upregulation of aquaporin 2 water channel expression in pregnant rats.
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.
Ohara
M
M
Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.
Martin
P Y
PY
Xu
D L
DL
St John
J
J
Pattison
T A
TA
Kim
J K
JK
Schrier
R W
RW
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
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