Roles of angiotensin II type 2 receptor in mice with fetal growth restriction.

Our previous report indicated that vascular injury enhances vascular remodeling in fetal growth restriction (FGR) mice. The angiotensin II type 2 receptor (AT2 R) is relatively highly expressed in fetal mice. Therefore, we investigated the roles of AT2 R in FGR-induced cardiovascular disease using AT2 R knockout (AT2 KO) mice. Dams (wild-type and AT2 KO mice) were fed an isocaloric diet containing 20% protein (NP) or 8% protein (LP) until delivery. Arterial blood pressure, body weight, and histological changes in organs were investigated in offspring. The birth weight of offspring from dams fed an LP diet (LPO) was significantly lower than that of offspring from dams fed an NP diet. The heart/body and kidney/body weight ratios in AT2 KO-LPO at 12 weeks of age were significantly higher than those in the other groups. Greater thickness of the left ventricular wall, larger cardiomyocyte size and enhancement of perivascular fibrosis were observed in AT2 KO-LPO. Interestingly, mRNA expression of collagen I and inflammatory cytokines was markedly higher in the AT2 KO-LPO heart at 6 weeks of age but not at 12 weeks of age. AT2 R signaling may be involved in cardiovascular disorders of adult offspring with FGR. Regulation of AT2 R could contribute to preventing future cardiovascular disease in FGR offspring.