Abstract P1103: Angiotensin II Type I Receptor Agonistic Autoantibody Blockade Improves Hypertension and Immune Activation in Postpartum Preeclamptic Rats

Abstract

Women with preeclampsia (PE) have a risk of developing cardiovascular diseases (CVD) later in life. The angiotensin II type I receptor agonistic autoantibodies (AT1-AAs) are elevated in women with PE, PE women 2 years post-partum (PP), and the reduced uterine perfusion pressure (RUPP) rat model of PE. Blockade of the AT1-AA by using a specific binding seven amino acid peptide sequence (7AA) improves the pathology of PE in RUPP rats. The long-term effects of AT1-AA inhibition on blood pressure, NK cell activation, heart mitochondria (mt) proteins, and CVD in the RUPP model PP is unknown. Therefore, we hypothesized that PP RUPP rats have elevated blood pressure, NK cell activation, and changes in heart mt proteins, which will be prevented in RUPP rats administered the 7AA during pregnancy. Methods: Pregnant Sprague Dawley rats were divided into groups; normal pregnant (NP) (n=7), RUPP (n=10), and RUPP+7AA (n=9). Gestational day 14, RUPP surgery was performed and 7AA (2 μg/ml) administered via minipump. Results: At 8 and 10 weeks (wks) PP, blood pressure (MAP), blood, and hearts were collected. NK cells were quantified by flow cytometry. At 8 wks PP, MAP was elevated in RUPP vs. NP (130±2 vs. 123±4 mmHg, ns), and RUPP+7AA (124±4 mmHg) treatment prevented this increase. At 10 wks, MAP was elevated in RUPP vs NP (133±5 vs. 120±5 mmHg, p=0.08), with a significant decrease in MAP in RUPP+7AA (107±6 mmHg) vs. RUPP (p<0.05). Total circulating NK cells were increased in RUPP vs NP (45±9. vs. 29± 8% gated cells, ns), which was prevented in RUPP+7AA (19±16 % gated cells) at 8 wks PP. Hearts were enlarged with RUPP vs NP (0.41±0.04 vs. 0.36±0.02g/100gBW, ns), which was normalized in RUPP+7AA (0.34±0.02g/100gBW). Previous studies show that during pregnancy complex IV is significantly lower along with a decrease mt function in RUPP vs NP. Complex IV mt proteins in the heart were elevated in RUPP+7AA vs. RUPP (5.5±1.7 vs. 3.0±0.2 AU, ns). Conclusion: In summary, PP PE rats have an increase in MAP, NK cells, and larger hearts. AT1-AA inhibition restores complex IV mt levels and improves HTN, immune activation, and cardiac hypertrophy PP. This study highlights the importance of AT1-AA inhibition during PE to prevent CVD later in life. Supported: AHA18CDA34110264