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

Tools

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., Vaka, V.R., McMaster, K., Ibrahim, T., Cornelius, D.C., Amaral, L., Campbell, N., Wallukat, G., McDuffy, S., Usry, N., 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

Repository Staff Only: item control page