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. 1998 Mar 1;101(5):1076–1083. doi: 10.1172/JCI649

Upregulation of aquaporin 2 water channel expression in pregnant rats.

M Ohara 1, P Y Martin 1, D L Xu 1, J St John 1, T A Pattison 1, J K Kim 1, R W Schrier 1
PMCID: PMC508659  PMID: 9486978

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.

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Selected References

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  1. Andersen L. J., Andersen J. L., Schütten H. J., Warberg J., Bie P. Antidiuretic effect of subnormal levels of arginine vasopressin in normal humans. Am J Physiol. 1990 Jul;259(1 Pt 2):R53–R60. doi: 10.1152/ajpregu.1990.259.1.R53. [DOI] [PubMed] [Google Scholar]
  2. Asahina Y., Izumi N., Enomoto N., Sasaki S., Fushimi K., Marumo F., Sato C. Increased gene expression of water channel in cirrhotic rat kidneys. Hepatology. 1995 Jan;21(1):169–173. [PubMed] [Google Scholar]
  3. Barron W. M., Dürr J., Stamoutsos B. A., Lindheimer M. D. Osmoregulation and vasopressin secretion during pregnancy in Brattleboro rats. Am J Physiol. 1985 Jan;248(1 Pt 2):R29–R37. doi: 10.1152/ajpregu.1985.248.1.R29. [DOI] [PubMed] [Google Scholar]
  4. Barron W. M., Lindheimer M. D. Osmoregulation in pseudopregnant and prolactin-treated rats: comparison with normal gestation. Am J Physiol. 1988 Mar;254(3 Pt 2):R478–R484. doi: 10.1152/ajpregu.1988.254.3.R478. [DOI] [PubMed] [Google Scholar]
  5. Burnette W. N. "Western blotting": electrophoretic transfer of proteins from sodium dodecyl sulfate--polyacrylamide gels to unmodified nitrocellulose and radiographic detection with antibody and radioiodinated protein A. Anal Biochem. 1981 Apr;112(2):195–203. doi: 10.1016/0003-2697(81)90281-5. [DOI] [PubMed] [Google Scholar]
  6. Chou C. L., DiGiovanni S. R., Luther A., Lolait S. J., Knepper M. A. Oxytocin as an antidiuretic hormone. II. Role of V2 vasopressin receptor. Am J Physiol. 1995 Jul;269(1 Pt 2):F78–F85. doi: 10.1152/ajprenal.1995.269.1.F78. [DOI] [PubMed] [Google Scholar]
  7. Chou C. L., DiGiovanni S. R., Mejia R., Nielsen S., Knepper M. A. Oxytocin as an antidiuretic hormone. I. Concentration dependence of action. Am J Physiol. 1995 Jul;269(1 Pt 2):F70–F77. doi: 10.1152/ajprenal.1995.269.1.F70. [DOI] [PubMed] [Google Scholar]
  8. Conrad K. P., Morganelli P. M., Brinck-Johnsen T., Colpoys M. C. The renin-angiotensin system during pregnancy in chronically instrumented, conscious rats. Am J Obstet Gynecol. 1989 Oct;161(4):1065–1072. doi: 10.1016/0002-9378(89)90785-0. [DOI] [PubMed] [Google Scholar]
  9. Davison J. M., Shiells E. A., Philips P. R., Lindheimer M. D. Serial evaluation of vasopressin release and thirst in human pregnancy. Role of human chorionic gonadotrophin in the osmoregulatory changes of gestation. J Clin Invest. 1988 Mar;81(3):798–806. doi: 10.1172/JCI113386. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Davison J. M., Vallotton M. B., Lindheimer M. D. Plasma osmolality and urinary concentration and dilution during and after pregnancy: evidence that lateral recumbency inhibits maximal urinary concentrating ability. Br J Obstet Gynaecol. 1981 May;88(5):472–479. doi: 10.1111/j.1471-0528.1981.tb01019.x. [DOI] [PubMed] [Google Scholar]
  11. DiGiovanni S. R., Nielsen S., Christensen E. I., Knepper M. A. Regulation of collecting duct water channel expression by vasopressin in Brattleboro rat. Proc Natl Acad Sci U S A. 1994 Sep 13;91(19):8984–8988. doi: 10.1073/pnas.91.19.8984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Durr J. A., Stamoutsos B., Lindheimer M. D. Osmoregulation during pregnancy in the rat. Evidence for resetting of the threshold for vasopressin secretion during gestation. J Clin Invest. 1981 Aug;68(2):337–346. doi: 10.1172/JCI110261. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Fitzsimons J. T., Simons B. J. The effect on drinking in the rat of intravenous infusion of angiotensin, given alone or in combination with other stimuli of thirst. J Physiol. 1969 Jul;203(1):45–57. doi: 10.1113/jphysiol.1969.sp008848. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Fushimi K., Uchida S., Hara Y., Hirata Y., Marumo F., Sasaki S. Cloning and expression of apical membrane water channel of rat kidney collecting tubule. Nature. 1993 Feb 11;361(6412):549–552. doi: 10.1038/361549a0. [DOI] [PubMed] [Google Scholar]
  15. Kim J. K., Summer S. N., Howard R. L., Schrier R. W. Vasopressin gene expression in rats with experimental cirrhosis. Hepatology. 1993 Jan;17(1):143–147. [PubMed] [Google Scholar]
  16. King L. S., Agre P. Pathophysiology of the aquaporin water channels. Annu Rev Physiol. 1996;58:619–648. doi: 10.1146/annurev.ph.58.030196.003155. [DOI] [PubMed] [Google Scholar]
  17. Kuwahara M., Fushimi K., Terada Y., Bai L., Marumo F., Sasaki S. cAMP-dependent phosphorylation stimulates water permeability of aquaporin-collecting duct water channel protein expressed in Xenopus oocytes. J Biol Chem. 1995 May 5;270(18):10384–10387. doi: 10.1074/jbc.270.18.10384. [DOI] [PubMed] [Google Scholar]
  18. Lindheimer M. D., Davison J. M. Osmoregulation, the secretion of arginine vasopressin and its metabolism during pregnancy. Eur J Endocrinol. 1995 Feb;132(2):133–143. doi: 10.1530/eje.0.1320133. [DOI] [PubMed] [Google Scholar]
  19. Nielsen S., Chou C. L., Marples D., Christensen E. I., Kishore B. K., Knepper M. A. Vasopressin increases water permeability of kidney collecting duct by inducing translocation of aquaporin-CD water channels to plasma membrane. Proc Natl Acad Sci U S A. 1995 Feb 14;92(4):1013–1017. doi: 10.1073/pnas.92.4.1013. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Nielsen S., DiGiovanni S. R., Christensen E. I., Knepper M. A., Harris H. W. Cellular and subcellular immunolocalization of vasopressin-regulated water channel in rat kidney. Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11663–11667. doi: 10.1073/pnas.90.24.11663. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Phippard A. F., Horvath J. S., Glynn E. M., Garner M. G., Fletcher P. J., Duggin G. G., Tiller D. J. Circulatory adaptation to pregnancy--serial studies of haemodynamics, blood volume, renin and aldosterone in the baboon (Papio hamadryas). J Hypertens. 1986 Dec;4(6):773–779. doi: 10.1097/00004872-198612000-00013. [DOI] [PubMed] [Google Scholar]
  22. Robson S. C., Hunter S., Boys R. J., Dunlop W. Serial study of factors influencing changes in cardiac output during human pregnancy. Am J Physiol. 1989 Apr;256(4 Pt 2):H1060–H1065. doi: 10.1152/ajpheart.1989.256.4.H1060. [DOI] [PubMed] [Google Scholar]
  23. Saito T., Ishikawa S. E., Sasaki S., Fujita N., Fushimi K., Okada K., Takeuchi K., Sakamoto A., Ookawara S., Kaneko T. Alteration in water channel AQP-2 by removal of AVP stimulation in collecting duct cells of dehydrated rats. Am J Physiol. 1997 Feb;272(2 Pt 2):F183–F191. doi: 10.1152/ajprenal.1997.272.2.F183. [DOI] [PubMed] [Google Scholar]
  24. Schrier R. W., Berl T., Anderson R. J. Osmotic and nonosmotic control of vasopressin release. Am J Physiol. 1979 Apr;236(4):F321–F332. doi: 10.1152/ajprenal.1979.236.4.F321. [DOI] [PubMed] [Google Scholar]
  25. Schrier R. W., Briner V. A. Peripheral arterial vasodilation hypothesis of sodium and water retention in pregnancy: implications for pathogenesis of preeclampsia-eclampsia. Obstet Gynecol. 1991 Apr;77(4):632–639. [PubMed] [Google Scholar]
  26. Uchida S., Sasaki S., Fushimi K., Marumo F. Isolation of human aquaporin-CD gene. J Biol Chem. 1994 Sep 23;269(38):23451–23455. [PubMed] [Google Scholar]
  27. Xu D. L., Martin P. Y., Ohara M., St John J., Pattison T., Meng X., Morris K., Kim J. K., Schrier R. W. Upregulation of aquaporin-2 water channel expression in chronic heart failure rat. J Clin Invest. 1997 Apr 1;99(7):1500–1505. doi: 10.1172/JCI119312. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Yamamoto T., Sasaki S., Fushimi K., Ishibashi K., Yaoita E., Kawasaki K., Marumo F., Kihara I. Vasopressin increases AQP-CD water channel in apical membrane of collecting duct cells in Brattleboro rats. Am J Physiol. 1995 Jun;268(6 Pt 1):C1546–C1551. doi: 10.1152/ajpcell.1995.268.6.C1546. [DOI] [PubMed] [Google Scholar]
  29. Yamamoto T., Sasaki S., Fushimi K., Kawasaki K., Yaoita E., Oota K., Hirata Y., Marumo F., Kihara I. Localization and expression of a collecting duct water channel, aquaporin, in hydrated and dehydrated rats. Exp Nephrol. 1995 May-Jun;3(3):193–201. [PubMed] [Google Scholar]
  30. Yasui M., Zelenin S. M., Celsi G., Aperia A. Adenylate cyclase-coupled vasopressin receptor activates AQP2 promoter via a dual effect on CRE and AP1 elements. Am J Physiol. 1997 Apr;272(4 Pt 2):F443–F450. doi: 10.1152/ajprenal.1997.272.4.F443. [DOI] [PubMed] [Google Scholar]

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