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Hypertension in Pregnancy Volume 39, 2020 - Issue 4
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Research Article

Tumor necrosis factor alpha (TNF-α) blockade improves natural killer cell (NK) activation, hypertension, and mitochondrial oxidative stress in a preclinical rat model of preeclampsia

Mark W. Cunninghama Department of Pharmacology & Toxicology, University of Mississippi Medical Center, Jackson, MS, USAView further author information
,
Aswathi Jayarama Department of Pharmacology & Toxicology, University of Mississippi Medical Center, Jackson, MS, USA;b Department of Obstetrics and Gynecology, University of Mississippi Medical Center, Jackson, MS, USAView further author information
,
Evangeline Deera Department of Pharmacology & Toxicology, University of Mississippi Medical Center, Jackson, MS, USAView further author information
,
Lorena M. Amarala Department of Pharmacology & Toxicology, University of Mississippi Medical Center, Jackson, MS, USAView further author information
,
Venkata Ramana Vakaa Department of Pharmacology & Toxicology, University of Mississippi Medical Center, Jackson, MS, USAView further author information
,
Tarek Ibrahima Department of Pharmacology & Toxicology, University of Mississippi Medical Center, Jackson, MS, USAView further author information
,
Denise C. Corneliusa Department of Pharmacology & Toxicology, University of Mississippi Medical Center, Jackson, MS, USA;c Department of Emergency Medicine, University of Mississippi Medical Center, Jackson, MS, USAView further author information
&
Babbette LaMarcaa Department of Pharmacology & Toxicology, University of Mississippi Medical Center, Jackson, MS, USA;b Department of Obstetrics and Gynecology, University of Mississippi Medical Center, Jackson, MS, USACorrespondence[email protected]
View further author information
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Pages 399-404 | Received 27 Apr 2020, Accepted 04 Jul 2020, Published online: 10 Jul 2020
 
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ABSTRACT

The RUPP rat model of Preeclampsia exhibits hypertension (MAP), cytolytic natural killer (cNK) cells, tumor necrosis factor alpha (TNF-α) and mitochondrial Reactive Oxygen Species (mt ROS).  Objective: Does TNF-α blockade with ETAN (Etanercept) decrease cNK cell and mt ROS in RUPP rats. Methods: On gestational day 14, RUPP surgery was performed, ETAN (0.4 mg/kg) was administered on day 18, MAP, blood and tissues collected on 19. Results:MAP, cytolytic NK cells and mt ROS were elevated in RUPP vs. NP and normalized with ETAN. Conclusion: TNF-α blockade lowered blood pressure and improve inflammation and organ function in response to placental ischemia.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This study was supported by NIH grant RO1HD067541 (BL), NIH grants R00HL130456 and P20GM104357 (DCC), NIH P20GM121334 (BL, LMA), American heart association (AHA) early career award 19CDA34670055 (LMA), and the AHA early career grant award 18CDA34110264 (MWCJr).

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