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IL-17-mediated oxidative stress is an important stimulator of AT1-AA and hypertension during pregnancy

Item Type:Article
Title:IL-17-mediated oxidative stress is an important stimulator of AT1-AA and hypertension during pregnancy
Creators Name:Dhillion, P. and Wallace, K. and Herse, F. and Scott, J. and Wallukat, G. and Heath, J. and Mosely, J. and Martin, J.N. and Dechend, R. and LaMarca, B.
Abstract:Preeclampsia is associated with autoimmune cells T(H)17, secreting interleukin-17, autoantibodies activating the angiotensin II type I receptor (AT1-AA), and placental oxidative stress (ROS). The objective of our study was to determine whether chronic IL-17 increases blood pressure by stimulating ROS and AT1-AAs during pregnancy. To answer this question four groups of rats were examined: normal pregnant (NP, n = 20), NP+IL-17 (n = 12), NP+tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl) (n = 7) (a superoxide dismutase mimetic that scavenges ROS), and NP+IL-17+tempol (n = 11). IL-17 (150 pg/day) was infused into NP rats while tempol was administered via the drinking water ad libitum. On day 19 blood pressure (MAP) was recorded, and plasma, urine, and tissue were collected for isolation of ROS detected by chemilluminescent technique. Urinary isoprostane was measured by ELISA. AT1-AAs were determined via cardiomyocyte assay and expressed as beats per minute. MAP increased from 98 +/- 3 mmHg in NP to 123 +/- 3 mmHg in IL-17-infused NP rats. Urinary isoprostane increased from 1,029 +/- 1 in NP to 3,526 +/- 2 pg.mg(-1).day(-1) in IL-17-infused rats (P < 0.05). Placental ROS was 436 +/- 4 RLU.ml(-1).min(-1) (n = 4) in NP and 702 +/- 5 (n = 5) RLU.ml(-1).min(-1) in IL-17-treated rats. Importantly, AT1-AA increased from 0.41 +/- 0.05 beats/min in NP rats (n = 8) to 18.4 +/- 1 beats/min in IL-17 rats (n = 12). Administration of tempol attenuated the hypertension (101 +/- 3 mmHg) ROS (459 +/- 5 RLU.ml(-1).min(-1)) and blunted AT1-AAs (7.3 +/- 0.6 beats/min) in NP+IL-17+tempol-treated rats. Additionally, AT1 receptor blockade inhibited IL-17-induced hypertension and placental oxidative stress. MAP was 105 +/- 5 mmHg and ROS was 418 +/- 5 RLU.ml(-1).min(-1) in NP+IL 17-treated with losartan. These data indicate that IL-17 causes placental oxidative stress, which serves as stimulus modulating AT1-AAs that may play an important role in mediating IL-17-induced hypertension during pregnancy.
Keywords:Autoimmunity, Preeclampsia, Reduced Uterine Perfusion Pressure, Animals, Rats
Source:American Journal of Physiology Regulatory Integrative and Comparative Physiology
ISSN:0363-6119
Publisher:American Physiological Society (U.S.A.)
Volume:303
Number:4
Page Range:R353-R358
Date:15 August 2012
Official Publication:https://doi.org/10.1152/ajpregu.00051.2012
PubMed:View item in PubMed

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