TY - JOUR
T1 - Role of mitochondrial dysfunction and reactive oxygen species in mediating hypertension in the reduced uterine perfusion pressure rat model of preeclampsia
AU - Vaka, Venkata Ramana
AU - McMaster, Kristen M.
AU - Cunningham, Mark W.
AU - Ibrahim, Tarek
AU - Hazlewood, Rebekah
AU - Usry, Nathan
AU - Cornelius, Denise C.
AU - Amaral, Lorena M.
AU - LaMarca, Babbette
N1 - Funding Information:
This research was supported by grants from the National Institutes of Health RO1HD067541 and P20GM121334 (B. LaMarca), HL130456 (D.C. Cornelius)/Office of Research, University of Mississippi Medical Center to B. LaMarca and 17PRE33660592/American Heart Association predoctoral fellowship to V.R. Vaka.
Funding Information:
We thank Dr Mike Murphy, PhD, MRC mitochondrial biology Unit, Cambridge UK for providing us with MitoQ. We thank Dr Robert Kramer for helping us with the optimization of mitochondrial assays. Dr Jon Hosler and Kristin Shirey, Department of Biochemistry, University of Mississippi Medical Center for their assistance with mitochondrial assays and analysis. This research was supported by grants from the National Institutes of Health RO1HD067541 and P20GM121334 (B. LaMarca), HL130456 (D.C. Cornelius)/Office of Research, University of Mississippi Medical Center to B. LaMarca and 17PRE33660592/American Heart Association predoctoral fellowship to V.R. Vaka.
Publisher Copyright:
© 2018 American Heart Association, Inc.
PY - 2018
Y1 - 2018
N2 - Placental ischemia is believed to be the initial event in the development of preeclampsia. Mitochondrial dysfunction is a cause of reactive oxygen species (ROS) generation and oxidative stress, however, there are not many studies examining the role of mitochondrial ROS in the pathology of preeclampsia. The purpose of this study was to not only examine the effect of placental ischemia on mitochondrial-mediated oxidative stress in reduced uterine perfusion pressure (RUPP) rat model of preeclampsia but to also examine the role of mitochondrial ROS in contributing to hypertension in response to placental ischemia. Female pregnant Sprague Dawley rats were used in this study. On gestational day 14, RUPP surgery was performed. On gestational day 19, blood pressure (mean arterial pressure) was measured, placentas and kidneys were collected from normal pregnant and RUPP rats and processed for mitochondrial respiration, ROS, and oxidative phosphorylation enzyme activities. Renal and placental complex activities, expressions and respiration rates were significantly reduced and mitochondrial ROS was increased in RUPP versus normal pregnant mitochondria. Mean arterial pressure was elevated in RUPP (n=6) compared with normal pregnant rats (n=5; 126±4 versus 103±4 mm Hg; P<0.05) and treatment with mitochondrial-specific antioxidants (MitoQ/MitoTEMPO) significantly reduced mean arterial pressure in RUPPs (n=5-10). Mitochondrial ROS was significantly elevated in endothelial cells incubated with RUPP serum compared from with normal pregnant rats, whereas serum from mito antioxidant-treated RUPP rats attenuated this response. Impaired mitochondrial function and vascular, placental, and renal mitochondrial ROS play an important role in hypertension and reduced fetal weight in response to placental ischemia during pregnancy.
AB - Placental ischemia is believed to be the initial event in the development of preeclampsia. Mitochondrial dysfunction is a cause of reactive oxygen species (ROS) generation and oxidative stress, however, there are not many studies examining the role of mitochondrial ROS in the pathology of preeclampsia. The purpose of this study was to not only examine the effect of placental ischemia on mitochondrial-mediated oxidative stress in reduced uterine perfusion pressure (RUPP) rat model of preeclampsia but to also examine the role of mitochondrial ROS in contributing to hypertension in response to placental ischemia. Female pregnant Sprague Dawley rats were used in this study. On gestational day 14, RUPP surgery was performed. On gestational day 19, blood pressure (mean arterial pressure) was measured, placentas and kidneys were collected from normal pregnant and RUPP rats and processed for mitochondrial respiration, ROS, and oxidative phosphorylation enzyme activities. Renal and placental complex activities, expressions and respiration rates were significantly reduced and mitochondrial ROS was increased in RUPP versus normal pregnant mitochondria. Mean arterial pressure was elevated in RUPP (n=6) compared with normal pregnant rats (n=5; 126±4 versus 103±4 mm Hg; P<0.05) and treatment with mitochondrial-specific antioxidants (MitoQ/MitoTEMPO) significantly reduced mean arterial pressure in RUPPs (n=5-10). Mitochondrial ROS was significantly elevated in endothelial cells incubated with RUPP serum compared from with normal pregnant rats, whereas serum from mito antioxidant-treated RUPP rats attenuated this response. Impaired mitochondrial function and vascular, placental, and renal mitochondrial ROS play an important role in hypertension and reduced fetal weight in response to placental ischemia during pregnancy.
KW - Antioxidants
KW - Blood pressure
KW - Ischemia
KW - Mitochondria
KW - Reactive oxygen species
UR - http://www.scopus.com/inward/record.url?scp=85055607619&partnerID=8YFLogxK
U2 - 10.1161/HYPERTENSIONAHA.118.11290
DO - 10.1161/HYPERTENSIONAHA.118.11290
M3 - Article
C2 - 30012871
AN - SCOPUS:85055607619
SN - 0194-911X
VL - 72
SP - 703
EP - 711
JO - Hypertension
JF - Hypertension
IS - 3
ER -