AT1-AA induced hypertension during pregnancy contributes to developmental programming of hypertension in female...

Preeclampsia (PE), new-onset hypertension during pregnancy, is accompanied by organ dysfunction, in addition to placental dysfunction, and is associated with chronic inflammation and fetal growth restriction. Agonistic autoantibodies against the angiotensin II type 1 receptor (AT1-AA) are produced in PE women and induce a PE-like phenotype when infused into pregnant rats. PE offspring are at higher risk for cardiovascular disease and hypertension; however, AT1-AA's role in these risks is unknown. Therefore, we hypothesized that AT1-AA exposure during pregnancy contributes to hypertension in adult offspring. We infused AT1-AA (1:40) starting on gestational day (GD) 14, allowed the dams to give birth, and birth weight was measured within 12 h. Offspring were aged to 4 months, one male and one female per litter were randomly selected to undergo carotid catheterization, mean arterial pressure (MAP) measurement, and blood and tissue collection. Female AT1-AA offspring had elevated MAP compared to control female offspring. Female AT1-AA offspring also had elevated progesterone, measured by mass spectroscopy, and renal endothelin-1, measured by RT-PCR and ELISA, compared to female control offspring. Male and female AT1-AA offspring had increased circulating AT1-AA, measured by cardiomyocyte bioassay, compared to male and female control offspring. These data demonstrate that AT1-AA infusion during pregnancy can predispose female offspring to have elevated blood pressure and persistently increased renal ET-1 and AT1-AA in adulthood.