UP-REGULATION OF AQUAPORIN-2 WATER CHANNEL EXPRESSION IN PREGNANT RATS

Water retention is characteristic of pregnancy bill the mechanism(s) o f the altered water metabolism has yet to be elucidated, The collectin g 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 o f AQP2 in papillae was examined, Nonpregnant (NP) littermates were use d as controls, Plasma osmolalities were significantly lower in pregnan t 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 mosmo l/kgH(2)O). However, plasma vasopressin concentrations in pregnant rat s 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 pr egnancy: AQP2 protein: P7 269 +/- 10.0, P14 251 +/- 12.0, ID < 0.0001, and P20 250 +/- 13.6%, P < 0.001 vs, NP (100 +/- 12.5%). The effect o f V2 vasopressin receptor ani agonist, OPC-31260, was then investigate d, 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 expre ssion 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 pregna ncy through a V2 receptor-mediated effect, In addition to vasopressin, other factors may be involved in this upregulation.