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An essential role for angiotensin II Type 1a receptor in pregnancy‐associated hypertension with intrauterine growth retardation
Author(s) -
Saito Tomoko,
Ishida Junji,
TakimotoOhnishi Eriko,
Takamine Shoko,
Shimizu Taku,
Sugaya Takeshi,
Kato Hideki,
Matsuoka Toshiki,
Nangaku Masaomi,
Kon Yasuhiro,
Sugiyama Fumihiro,
Yagami Kenichi,
Fukamizu Akiyoshi
Publication year - 2004
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.03-0321fje
Subject(s) - medicine , endocrinology , angiotensin ii receptor type 1 , renin–angiotensin system , pregnancy , angiotensin ii , fetus , receptor , plasma renin activity , blood pressure , biology , genetics
Little is known about an in vivo significance of angiotensin II Type‐1 receptor (AT1) for pregnancy‐associated diseases, including hypertension and intrauterine growth retardation (IUGR). We previously demonstrated that female mice carrying the human angiotensinogen gene (hAG +/+ ), when mated with human renin transgenic (hRN +/+ ) male mice, displayed hypertension in late pregnancy due to secretion of human renin from the fetal side into the maternal circulation. In the present study, to investigate a role for AT1 in pregnancy‐associated hypertension, we generated a new strain of hAG +/+ /mAT1a −/− mice by genetically deleting the AT1a gene from hAG +/+ mice. When mated with hRN +/+ male mice, excessive increases in human renin, angiotensin, and plasma renin activity were detected in the plasma of pregnant hAG +/+ /mAT1a −/− mice as found in that of pregnant hAG +/+ mice. Surprisingly, however, blood pressure of hAG +/+ /mAT1a −/− mice was not elevated in late pregnancy despite the presence of AT1b, a subtype of AT1. The maternal and fetal defects, such as cardiac and placental abnormalities, and IUGR observed in pregnant hypertensive hAG +/+ mice were not recognized in pregnant hAG +/+ /mAT1a −/− mice. The limited term administration of AT1 antagonists to hypertensive hAG +/+ mice in late pregnancy dramatically improved hypertension and IUGR, showing the clinical importance of AT1a.