Key result
Maternal AT1-AA exposure increases adult female offspring mean arterial pressure by ~14 mmHg.
Why the study?
Preeclampsia offspring have a higher risk of cardiovascular disease and hypertension, but the role of AT1-AA exposure during pregnancy in conferring these risks was unknown.
Does AT1-AA exposure during pregnancy cause long-term AT1-AA production and hypertension in adult offspring?
Does AT1-AA exposure during pregnancy cause long-term AT1-AA production and hypertension in adult offspring?
Absolute Event Rate: 124% vs 110%
p-value: p=<0.05
Perinatal AT1-AA exposure causes long-term AT1-AA production in all offspring and hypertension in female offspring, highlighting a potential mechanism for familial risk of preeclampsia and cardiovascular disease.
May program hypertension in female offspring; leaves open intergenerational AT1-AA role in human preeclampsia-related CVD.
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 hours. 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. • We show that perinatal AT1-AA exposure causes long-term AT1-AA production and hypertension in female offspring. • Preeclampsia is associated with increased risk for disease in offspring, including hypertension. AT1-AA may be one factor produced in preeclamptic patients that confers elevated risk to female offspring. • Targeting AT1-AA during pregnancy or in children from preeclamptic pregnancies may improve long-term health
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Campbell et al. (2025) studied Developmental programming of hypertension (Preeclampsia model) (n=30). AT1-AA vs. Saline was evaluated on Mean arterial pressure (MAP) in female offspring at 4 months (p=<0.05). Maternal infusion of AT1-AA during pregnancy significantly increased mean arterial pressure in adult female offspring to 124 mmHg compared to 110 mmHg in controls (p < 0.05).
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