Undernutrition in utero augments systolic blood pressure and cardiac remodeling in adult mouse offspring:: Possible involvement of local cardiac angiotensin system in developmental origins of cardiovascular disease

Evidence has emerged that undernutrition in utero is a risk factor for cardiovascular disorders in adulthood, along with genetic and environmental factors. Recently, the local expression of angiotensinogen and related bioactive substances has been demonstrated to play a pivotal role in cardiac remodeling, i.e. fibrosis and hypertrophy. The aim of the present study was to clarify the possible involvement of the local cardiac angiotensin system in fetal undernutrition-induced cardiovascular disorders. We developed a mouse model of undernutrition in utero by maternal food restriction, in which offspring ( UN offspring) showed an increase in systolic blood pressure ( 8 wk of age, P < 0.05; and 16 wk, P < 0.01), perivascular fibrosis of the coronary artery ( 16 wk, P < 0.05) and cardiac cardiomegaly ( 16 wk, P < 0.01), and cardiomyocyte enlargement, concomitant with a significant augmentation of angiotensinogen ( P < 0.05) and endothelin-1 ( P < 0.01) mRNA expression and a tendency to increase in immunostaining for both angiotensin II and endothelin-1 in the left ventricles ( 16 wk). These findings suggest that fetal undernutrition activated the local cardiac angiotensin system-associated bioactive substances, which contributed, at least partly, to the development of cardiac remodeling in later life, in concert with the effects of increase in blood pressure.