Abstract P307: Renal Natural Killer Cell Activation and Mitochondrial Oxidative Stress; New Mechanisms in AT1-AA Mediated Hypertensive Pregnancy

Abstract

Women with preeclampsia (PE) have increased blood pressure (MAP), natural killer (NK) cells, reactive oxygen species (ROS), and agonistic autoantibodies to the angiotensin II type 1 receptor (AT1-AA). AT1-AA’s administered to pregnant rodents produces a well-accepted model of PE. However, the role of NK cells and mitochondrial reactive oxygen species (mtROS) in AT1-AA mediated hypertension during pregnancy is unknown. We hypothesize that AT1-AA induced model of PE will exhibit elevated MAP, NK cells, and mtROS; while inhibition of the AT1-AA binding to the AT1R would be preventative. Pregnant rats were divided into 3 groups: normal pregnant (NP) (n=5), NP + AT1-AA infused (NP + AT1-AA) (n= 10), and NP + AT1-AA + AT1-AA inhibitory peptide (NP + AT1-AA + ‘n7AAc’) (n=8). Day 13, rats were surgically administered mini-pumps with either AT1-AA or AT1-AA+‘n7AAc’. Day 19, tissue and blood was collected. MAP was elevated in AT1-AA vs. NP (119±1 vs. 102±2 mmHg, p<0.05) and was prevented by ‘n7AAc’ (108±3). There was a 6 fold increase in renal activated NK cells in AT1-AA vs .NP (1.2±0.4 vs. 0.2±0.1 % Gated, p=0.05) and a return to NP levels in AT1-AA +‘n7AAc’ (0.1±0.1 % Gated). Renal mtROS (317±49 vs. 101±13 % Fold, p<0.05) was elevated with AT1-AA vs NP and was decreased in AT1-AA +‘n7AAc’ (128±16, p<0.05). AT1-AA’s infused into pregnant rats increased MAP, NK cells, and mtROS which were prevented by AT1-AA inhibition, thus highlighting new mechanisms of AT1-AA and the importance of drug therapy targeted to AT1-AAs in hypertensive pregnancies. Research Supported by NIH grants HL78147, HL51971, and HD067541 awarded to BL. DC is supported by NIH grant HL130456 and the American Heart Association 16SDG27520000.