Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Science 8 November 1996:
Vol. 274. no. 5289, pp. 995 - 998
DOI: 10.1126/science.274.5289.995

Reports

Hypertension Induced in Pregnant Mice by Placental Renin and Maternal Angiotensinogen

Eriko Takimoto, Junji Ishida, Fumihiro Sugiyama, Hisashi Horiguchi, Kazuo Murakami, Akiyoshi Fukamizu *

Maternal hypertension is a common complication of pregnancy and its pathophysiology is poorly understood. This phenomenon was studied in an animal model by mating transgenic mice expressing components of the human renin-angiotensin system. When transgenic females expressing angiotensinogen were mated with transgenic males expressing renin, the pregnant females displayed a transient elevation of blood pressure in late pregnancy, due to secretion of placental human renin into the maternal circulation. Blood pressure returned to normal levels after delivery of the pups. Histopathologic examination revealed uniform enlargement of glomeruli associated with an increase in urinary protein excretion, myocardial hypertrophy, and necrosis and edema in the placenta. These mice may provide molecular insights into pregnancy-associated hypertension in humans.

E. Takimoto, J. Ishida, K. Murakami, A. Fukamizu, Institute of Applied Biochemistry and Tsukuba Advanced Research Alliance (TARA), University of Tsukuba, Ibaraki 305, Japan.
F. Sugiyama, Laboratory Animal Research Center, University of Tsukuba, Ibaraki 305, Japan.
H. Horiguchi, Institute of Basic Medical Sciences, University of Tsukuba, Ibaraki 305, Japan.
*   To whom correspondence should be addressed. E-mail: akif{at}sakura.cc.tsukuba.ac.jp


Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Mice Overexpressing Both Human Angiotensinogen and Human Renin as a Model of Superimposed Preeclampsia on Chronic Hypertension.
S. Falcao, E. Stoyanova, G. Cloutier, R. L. Maurice, J. Gutkowska, and J. L. Lavoie (2009)
Hypertension 54, 1401-1407
   Abstract »    Full Text »    PDF »
The detrimental role of angiotensin receptor agonistic autoantibodies in intrauterine growth restriction seen in preeclampsia.
R. A. Irani, Y. Zhang, S. C. Blackwell, C. C. Zhou, S. M. Ramin, R. E. Kellems, and Y. Xia (2009)
J. Exp. Med. 206, 2809-2822
   Abstract »    Full Text »    PDF »
Peptide Hormone Regulation of Angiogenesis.
C. Clapp, S. Thebault, M. C. Jeziorski, and G. Martinez De La Escalera (2009)
Physiol Rev 89, 1177-1215
   Abstract »    Full Text »    PDF »
The Importance of Angiotensin II Subtype Receptors for Blood Pressure Control During Mouse Pregnancy.
Kai Chen, D. C. Merrill, and J. C. Rose (2007)
Reproductive Sciences 14, 694-704
   Abstract »    PDF »
Potential Roles of Angiotensin Receptor-Activating Autoantibody in the Pathophysiology of Preeclampsia.
Y. Xia, S. M. Ramin, and R. E. Kellems (2007)
Hypertension 50, 269-275
   Full Text »    PDF »
Genome-wide expression profiling of placentas in the p57Kip2 model of pre-eclampsia.
K.S. Knox and J.C. Baker (2007)
Mol. Hum. Reprod. 13, 251-263
   Abstract »    Full Text »    PDF »
Angiotensin II decreases system A amino acid transporter activity in human placental villous fragments through AT1 receptor activation.
E. Shibata, R. W. Powers, A. Rajakumar, F. von Versen-Hoynck, M. J. Gallaher, D. L. Lykins, J. M. Roberts, and C. A. Hubel (2006)
Am J Physiol Endocrinol Metab 291, E1009-E1016
   Abstract »    Full Text »    PDF »
Differential Roles of Renin and Angiotensinogen in the Feto-Maternal Interface in the Development of Complications of Pregnancy.
E. Takimoto-Ohnishi, T. Saito, J. Ishida, J. Ohnishi, F. Sugiyama, K.-I. Yagami, and A. Fukamizu (2005)
Mol. Endocrinol. 19, 1361-1372
   Abstract »    Full Text »    PDF »
Role of the renin-angiotensin system in the pathogenesis of preeclampsia.
D. M. Shah (2005)
Am J Physiol Renal Physiol 288, F614-F625
   Abstract »    Full Text »    PDF »
Agonistic Autoantibodies to the AT1 Receptor in a Transgenic Rat Model of Preeclampsia.
R. Dechend, P. Gratze, G. Wallukat, E. Shagdarsuren, R. Plehm, J.-H. Brasen, A. Fiebeler, W. Schneider, S. Caluwaerts, L. Vercruysse, et al. (2005)
Hypertension 45, 742-746
   Abstract »    Full Text »    PDF »
Pregnancy-Induced Alterations of Vascular Function in Mouse Mesenteric and Uterine Arteries.
C.-L. M. Cooke and S. T. Davidge (2003)
Biol Reprod 68, 1072-1077
   Abstract »    Full Text »    PDF »
Role of AT2 receptor in the brain in regulation of blood pressure and water intake.
Z. Li, M. Iwai, L. Wu, T. Shiuchi, T. Jinno, T.-X. Cui, and M. Horiuchi (2003)
Am J Physiol Heart Circ Physiol 284, H116-H121
   Abstract »    Full Text »    PDF »
Resistance to Neointimal Hyperplasia and Fatty Streak Formation in Mice With Adrenomedullin Overexpression.
Y. Imai, T. Shindo, K. Maemura, M. Sata, Y. Saito, Y. Kurihara, M. Akishita, J. Osuga, S. Ishibashi, K. Tobe, et al. (2002)
Arterioscler Thromb Vasc Biol 22, 1310-1315
   Abstract »    Full Text »    PDF »
Discovery of a Spontaneous Genetic Mouse Model of Preeclampsia.
R. L. Davisson, D. S. Hoffmann, G. M. Butz, G. Aldape, G. Schlager, D. C. Merrill, S. Sethi, R. M. Weiss, and J. N. Bates (2002)
Hypertension 39, 337-342
   Abstract »    Full Text »    PDF »
Pregnancy-Induced Changes in Renin Gene Expression in Mice.
Y. Xia, H. Wen, H. R. Prashner, R. Chen, T. Inagami, D. F. Catanzaro, and R. E. Kellems (2002)
Biol Reprod 66, 135-143
   Abstract »    Full Text »
Paternal and Maternal Components of the Predisposition to Preeclampsia.
M. S. Esplin, M. B. Fausett, A. Fraser, R. Kerber, G. Mineau, J. Carrillo, and M. W. Varner (2001)
N. Engl. J. Med. 344, 867-872
   Abstract »    Full Text »    PDF »
Long-term telemetric measurement of cardiovascular parameters in awake mice: a physiological genomics tool.
G. M. BUTZ and R. L. DAVISSON (2001)
Physiol Genomics 5, 89-97
   Abstract »    Full Text »    PDF »
Endothelial-derived nitric oxide and angiotensinogen: blood pressure and metabolism during mouse pregnancy.
L. A. Hefler, C. B. Tempfer, R. M. Moreno, W. E. O'Brien, and A. R. Gregg (2001)
Am J Physiol Regulatory Integrative Comp Physiol 280, R174-R182
   Abstract »    Full Text »    PDF »
Rats Transgenic for Human Renin and Human Angiotensinogen as a Model for Gestational Hypertension.
J. BOHLENDER, D. GANTEN, and F. C. LUFT (2000)
J. Am. Soc. Nephrol. 11, 2056-2061
   Abstract »    Full Text »
Definitive Molecular Evidence of Renin-Angiotensin System in Human Uterine Decidual Cells.
C. Li, R. Ansari, Z. Yu, and D. Shah (2000)
Hypertension 36, 159-164
   Abstract »    Full Text »    PDF »
Preeclampsia Prevention and Management.
E. R. Norwitz and J. T. Repke (2000)
Reproductive Sciences 7, 21-36
   Abstract »    PDF »
Highly Regulated Cell Type-restricted Expression of Human Renin in Mice Containing 140- or 160-Kilobase Pair P1 Phage Artificial Chromosome Transgenes.
P. L. Sinn, D. R. Davis, and C. D. Sigmund (1999)
J. Biol. Chem. 274, 35785-35793
   Abstract »    Full Text »    PDF »
Human Spiral Artery Renin-Angiotensin System.
T. Morgan, C. Craven, and K. Ward (1998)
Hypertension 32, 683-687
   Abstract »    Full Text »    PDF »
Fetal and maternal contributions to risk of pre-eclampsia: population based study.
R. T. Lie, S. Rasmussen, H. Brunborg, H. K Gjessing, E. Lie-Nielsen, and L. M Irgens (1998)
BMJ 316, 1343-1347
   Abstract »    Full Text »
From Genetically Altered Mice to Integrative Physiology.
M. Gassmann and T. Hennet (1998)
Physiology 13, 53-57
   Abstract »    Full Text »    PDF »
Molecular Genetics of Human Hypertension: Role of Angiotensinogen.
P. Corvol and X. Jeunemaitre (1997)
Endocr. Rev. 18, 662-677
   Abstract »    Full Text »



To Advertise     Find Products


Science. ISSN 0036-8075 (print), 1095-9203 (online)