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 (AT₂R) is relatively highly expressed in fetal mice. Therefore, we investigated the roles of AT₂R in FGR-induced cardiovascular disease using AT₂R knockout (AT₂KO) mice. Dams (wild-type and AT₂KO 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 AT₂KO-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 AT₂KO-LPO. Interestingly, mRNA expression of collagen I and inflammatory cytokines was markedly higher in the AT₂KO-LPO heart at 6 weeks of age but not at 12 weeks of age. AT₂R signaling may be involved in cardiovascular disorders of adult offspring with FGR. Regulation of AT₂R could contribute to preventing future cardiovascular disease in FGR offspring.