| First Author | Saito T | Year | 2004 |
| Journal | FASEB J | Volume | 18 |
| Issue | 2 | Pages | 388-90 |
| PubMed ID | 14688210 | Mgi Jnum | J:127914 |
| Mgi Id | MGI:3765210 | Doi | 10.1096/fj.03-0321fje |
| Citation | Saito T, et al. (2004) An essential role for angiotensin II type 1a receptor in pregnancy-associated hypertension with intrauterine growth retardation. FASEB J 18(2):388-90 |
| abstractText | 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. |
