The pathophysiological study of pregnancy induced hypertension in transgenic mice carrying both human renin and angiotensinogen genes

2005 Fiscal Year Final Research Report Summary

• Project/Area Number: 15591790
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Kurume University
• Principal Investigator: MIFUNE Hiroharu Kurume University, Medicine, Assistant Professor, 医学部, 講師 (70174117)
• Co-Investigator(Kenkyū-buntansha): HORI Daizo Kurume University, Medicine, Associate Professor, 医学部, 助教授 (80157049) ; NONOSHITA Akiko Kurume University, Medicine, Assistant, 医学部, 助手 (00309832) ; NAGAYAMA Sachiyo Kurume University, Medicine, Assistant, 医学部, 助手 (20309834) ; KITADA Masae Kurume University, Medicine, Assistant, 医学部, 助手 (90341354)
• Project Period (FY): 2003 – 2005
• Keywords: pregnancy-induced hypertension / transgenic mouse / rennin angiotensin system / antihypertension / quinapril / candesartan cilexetil / hydralazine / nicardipine

Research Abstract

Objectives : The aim of this study is to analyze pathophysiological changes in pregnancy-induced hypertension (PIH) by cross-mating transgenic mice carrying the human-angiotensinogen gene with mice bearing the human-renin gene. Further, we examined antihypertensive effects of four drugs in PIH model mice.
Materials and Methods : The systolic blood pressure was measured by the tail-cuff method during the early, mid, and late periods of pregnancy in the transgenic mice and the wild type as control mice. The fetus, placenta, maternal kidney, heart and blood were obtained from the pregnant mice on 18^<th> day of gestation, and then the concentrations of human(h)-renin and angiotensin (AT) II in those materials were measured by radioimmunoassay. Further, the changes of systolic blood pressure and fetal weight in PIH model mice after oral administration of quinapril, candesartan cilexetil, hydralazine and nicardipine were analyzed.
Results : In the transgenic mice, the systolic blood pressure began to rise at mid period of gestation, and reached high level in the day before delivery. The hypertension during pregnancy returned to healthy level after delivery. The kidney and fetal weight in the transgenic mice were significantly lower than those in the wild type, but there was no difference in the heart and the placental weight. The hypertension and lower fetal weigh in PIH model mice were improved by oral administration of quinapril and candesartan cilexetil. In the transgenic mice, the h-renin was only detected in the placenta and maternal plasma, and the concentrations of the placental and plasma AT II were significantly higher than those in control mice.
Conclusions : Our study showed that the redundant increase of the concentrations of the placental and plasma h-renin and AT II caused hypertension in late period of pregnancy in the transgenic mice.