Renal natural killer cell activation and mitochondrial oxidative stress; new mechanisms in AT1-AA mediated hypertensive pregnancy

Item Type:	Article
Title:	Renal natural killer cell activation and mitochondrial oxidative stress; new mechanisms in AT1-AA mediated hypertensive pregnancy
Creators Name:	Cunningham, M.W. and Vaka, V.R. and McMaster, K. and Ibrahim, T. and Cornelius, D.C. and Amaral, L. and Campbell, N. and Wallukat, G. and McDuffy, S. and Usry, N. and Dechend, R. and LaMarca, B.
Abstract:	Women with preeclampsia (PE) have increased mean arterial 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 4 groups: normal pregnant (NP) (n = 5), NP + AT1-AA inhibitory peptide (NP +‘n7AAc’) (n = 3), NP + AT1-AA infused (NP + AT1-AA) (n = 10), and NP + AT1-AA +‘n7AAc’ (n = 8). Day 13, rats were surgically implanted with mini-pumps infusing 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 this 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) which returned 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). In conclusion, AT1-AA’s increased MAP, NK cells, and mtROS which were attenuated by AT1-AA inhibition, thus highlighting new mechanisms of AT1-AA and the importance of drug therapy targeted to AT1-AAs in hypertensive pregnancies.
Keywords:	Preeclampsia, AT1-AA, Mitochondrial ROS, Natural Killer Cells, Hypertension, Animals, Rats
Source:	Pregnancy Hypertension
ISSN:	2210-7789
Publisher:	Elsevier
Volume:	15
Page Range:	72-77
Date:	January 2019
Official Publication:	https://doi.org/10.1016/j.preghy.2018.11.004
External Fulltext:	View full text on PubMed Central
PubMed:	View item in PubMed

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