AT1-AA Induced Hypertension During Pregnancy Contributes to Developmental Programming of Hypertension in Female Offspring

Authors

Nathan Campbell, University of Mississippi Medical Center
James P. Lemon, University of Mississippi Medical Center
Melissa Helmich, University of Mississippi Medical Center
Dylan Solise, University of Mississippi Medical Center
Alexandra Demesa, University of Mississippi Medical Center
Ella Goolsby, University of Mississippi Medical Center
Evan LaMarca, University of Mississippi Medical Center
Evangeline Deer, University of Mississippi Medical Center
Denise C. Cornelius, University of Mississippi Medical Center
Ty Turner, University of Mississippi Medical Center
Lorena M. Amaral, University of Mississippi Medical Center
Baoying Zheng, University of Mississippi Medical Center
Babbette LaMarca, University of Mississippi Medical Center

Author Type

faculty

Document Type

Article

Source Publication Title

Journal of Reproductive Immunology

Abstract

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.

DOI

https://doi.org/10.1016/j.jri.2025.104802

Publication Date

11-22-2025

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.

Recommended Citation

Campbell, Nathan; Lemon, James P.; Helmich, Melissa; Solise, Dylan; Demesa, Alexandra; Goolsby, Ella; LaMarca, Evan; Deer, Evangeline; Cornelius, Denise C.; Turner, Ty; Amaral, Lorena M.; Zheng, Baoying; and LaMarca, Babbette, "AT1-AA Induced Hypertension During Pregnancy Contributes to Developmental Programming of Hypertension in Female Offspring" (2025). Pharmacology and Toxicology. 1.
https://digitalcollections.umc.edu/pharmapub/1