Angiotensin II type 1 receptor agonistic autoantibody blockade improves postpartum hypertension and cardiac mitochondrial function in rat model of preeclampsia

Biology of Sex Differences

Jonathan P. Hosler¹  Ngoc H. Hoang¹  Michael Bowling²  George W. Booz²  Daniel Kennedy²  Taprieka Robinson²  Daniel Azubuike²  Brandon Fisher²  Karen Brooks²  Pooja Chinthakuntla²  Mark W. Cunningham³ 

[1] Department of Cell and Molecular Biology, University of Mississippi Medical Center, Jackson, MS, USA;Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS, USA;Department of Physiology and Anatomy, University of North Texas Health Science Center, 3500 Camp Bowie Boulevard, 76107, Fort Worth, TX, USA;

关键词: Postpartum;    Hypertension;    Cardiac mitochondrial function;    Cardiovascular disease;    Preeclampsia;   

DOI  :  10.1186/s13293-021-00396-x

来源: Springer

【 摘 要 】

Women with preeclampsia (PE) have a greater risk of developing hypertension, cardiovascular disease (CVD), and renal disease later in life. Angiotensin II type I receptor agonistic autoantibodies (AT1-AAs) are elevated in women with PE during pregnancy and up to 2-year postpartum (PP), and in the reduced uterine perfusion pressure (RUPP) rat model of PE. Blockade of AT1-AA with a specific 7 amino acid peptide binding sequence (‘n7AAc’) improves pathophysiology observed in RUPP rats; however, the long-term effects of AT1-AA inhibition in PP is unknown. Pregnant Sprague Dawley rats were divided into three groups: normal pregnant (NP) (n = 16), RUPP (n = 15), and RUPP + ‘n7AAc’ (n = 16). Gestational day 14, RUPP surgery was performed and ‘n7AAc’ (144 μg/day) administered via osmotic minipump. At 10-week PP, mean arterial pressure (MAP), renal glomerular filtration rate (GFR) and cardiac functions, and cardiac mitochondria function were assessed. MAP was elevated PP in RUPP vs. NP (126 ± 4 vs. 116 ± 3 mmHg, p < 0.05), but was normalized in in RUPP + ‘n7AAc’ (109 ± 3 mmHg) vs. RUPP (p < 0.05). PP heart size was reduced by RUPP + ’n7AAc’ vs. RUPP rats (p < 0.05). Complex IV protein abundance and enzymatic activity, along with glutamate/malate-driven respiration (complexes I, III, and IV), were reduced in the heart of RUPP vs. NP rats which was prevented with ‘n7AAc’. AT1-AA inhibition during pregnancy not only improves blood pressure and pathophysiology of PE in rats during pregnancy, but also long-term changes in blood pressure, cardiac hypertrophy, and cardiac mitochondrial function PP.

【 授权许可】

CC BY