Tumor Necrosis Factor-alpha Blockade Improves Uterine Artery Resistance, Maternal Blood Pressure, and Fetal Growth in Placental Ischemic Rats
| Autor: | Jan M. Williams, Andrea K Brown, Geilda A. Tardo, Tyler Johnson, Chelsea Giachelli, Denise C. Cornelius, Madison T. Crosby, Olivia K. Travis, Shani Siddiq, Henry T. Nguyen |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_specialty
Mean arterial pressure Placenta Intrauterine growth restriction 030204 cardiovascular system & hematology Article Preeclampsia Nitric oxide Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Pregnancy Internal medicine medicine.artery Internal Medicine medicine Animals Humans Arterial Pressure Uterine artery Fetus Fetal Growth Retardation 030219 obstetrics & reproductive medicine Tumor Necrosis Factor-alpha business.industry Uterus Obstetrics and Gynecology medicine.disease Rats Blockade Disease Models Animal Oxidative Stress Uterine Artery Endocrinology chemistry Gestation Female business |
| Zdroj: | Pregnancy Hypertens |
| ISSN: | 2210-7789 |
| DOI: | 10.1016/j.preghy.2021.05.002 |
| Popis: | We recently reported that adoptive transfer of cytolytic Natural Killer cells (cNKs) from the Reduced Uterine Perfusion Pressure (RUPP) rat induces a preeclampsia (PE)-like phenotype in pregnant rats, accompanied by increased TNF-α. The purpose of this study was to investigate a role for increased TNF-α to induce oxidative stress (ROS), decrease nitric oxide (NO) bioavailability, and induce vascular dysfunction as mechanisms of hypertension (HTN) and intrauterine growth restriction (IUGR) in RUPPs. Pregnant Sprague Dawley rats underwent the RUPP or a Sham procedure on gestation day (GD) 14. On GDs 15 and 18, a subset of Sham and RUPP rats received i.p.injections of vehicle or 0.4 mg/kg of Etanercept (ETA), a soluble TNF-α receptor (n = 10/group). On GD18, Uterine Artery Resistance Index (UARI) was measured, and on GD19, mean arterial pressure (MAP), fetal and placental weights were measured, and blood and tissues were processed for analysis. TNF-α blockade normalized the elevated MAP observed RUPP. Additionally, both fetal and placental weights were decreased in RUPP compared to Sham, and were normalized in RUPP + ETA. Placental ROS was also increased in RUPP rats compared to Sham, and remained elevated in RUPP + ETA. Compared to Sham, UARI was elevated in RUPPs while plasma total nitrate was reduced, and these were normalized in ETA treated RUPPs. In conclusion, TNF-α blockade in RUPPs reduced MAP and UARI, improved fetal growth, and increased NO bioavailability. These data suggest that TNF-α regulation of NO bioavailability is a potential mechanism that contributes to PE pathophysiology and may represent a therapeutic target to improve maternal outcomes and fetal growth. |
| Databáze: | OpenAIRE |
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