PMID- 35624708
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220716
IS  - 2076-3921 (Print)
IS  - 2076-3921 (Electronic)
IS  - 2076-3921 (Linking)
VI  - 11
IP  - 5
DP  - 2022 Apr 26
TI  - Activation of Nrf2 in Mice Causes Early Microvascular Cyclooxygenase-Dependent 
      Oxidative Stress and Enhanced Contractility.
LID - 10.3390/antiox11050845 [doi]
LID - 845
AB  - Nuclear factor erythroid factor E2-related factor 2 (Nrf2) transcribes 
      antioxidant genes that reduce the blood pressure (BP), yet its activation with 
      tert-butylhydroquinone (tBHQ) in mice infused with angiotensin II (Ang II) 
      increased mean arterial pressure (MAP) over the first 4 days of the infusion. 
      Since tBHQ enhanced cyclooxygenase (COX) 2 expression in vascular smooth muscle 
      cells (VSMCs), we tested the hypothesis that tBHQ administration during an 
      ongoing Ang II infusion causes an early increase in microvascular COX-dependent 
      reactive oxygen species (ROS) and contractility. Mesenteric microarteriolar 
      contractility was assessed on a myograph, and ROS by RatioMaster. Three days of 
      oral tBHQ administration during the infusion of Ang II increased the mesenteric 
      microarteriolar mRNA for p47(phox), the endothelin type A receptor and 
      thromboxane A(2) synthase, and increased the excretion of 8-isoprostane F(2alpha) and 
      the microarteriolar ROS and contractions to a thromboxane A(2) (TxA(2)) agonist 
      (U-46,619) and endothelin 1 (ET1). These were all prevented in Nrf2 knockout 
      mice. Moreover, the increases in ROS and contractility were prevented in COX1 
      knockout mice with blockade of COX2 and by blockade of thromboxane prostanoid 
      receptors (TPRs). In conclusion, the activation of Nrf2 over 3 days of Ang II 
      infusion enhances microarteriolar ROS and contractility, which are dependent on 
      COX1, COX2 and TPRs. Therefore, the blockade of these pathways may diminish the 
      early adverse cardiovascular disease events that have been recorded during the 
      initiation of Nrf2 therapy.
FAU - Wang, Dan
AU  - Wang D
AUID- ORCID: 0000-0002-0302-9824
AD  - Division of Nephrology and Hypertension and Hypertension Center, Georgetown 
      University, Washington, DC 20007, USA.
FAU - Wang, Cheng
AU  - Wang C
AD  - Division of Nephrology, Department of Medicine, The Fifth Affiliated Hospital of 
      Sun Yat-sen University, Zhuhai 519000, China.
FAU - Hao, Xueqin
AU  - Hao X
AD  - Department of Human Anatomy and Histoembryology, School of Basic Medical 
      Sciences, Henan University of Science and Technology, Luoyang 471023, China.
FAU - Carter, Gabriela
AU  - Carter G
AD  - Division of Nephrology and Hypertension and Hypertension Center, Georgetown 
      University, Washington, DC 20007, USA.
FAU - Carter, Rafaela
AU  - Carter R
AD  - Division of Nephrology and Hypertension and Hypertension Center, Georgetown 
      University, Washington, DC 20007, USA.
FAU - Welch, William J
AU  - Welch WJ
AD  - Division of Nephrology and Hypertension and Hypertension Center, Georgetown 
      University, Washington, DC 20007, USA.
FAU - Wilcox, Christopher S
AU  - Wilcox CS
AD  - Division of Nephrology and Hypertension and Hypertension Center, Georgetown 
      University, Washington, DC 20007, USA.
LA  - eng
GR  - RO-1 DK109272; PO-1, HL068686; RO1-HL134511/NH/NIH HHS/United States
PT  - Journal Article
DEP - 20220426
PL  - Switzerland
TA  - Antioxidants (Basel)
JT  - Antioxidants (Basel, Switzerland)
JID - 101668981
PMC - PMC9137799
OTO - NOTNLM
OT  - bardoxolone methyl
OT  - endothelin
OT  - hypertension
OT  - tert-butylhydroxyquinone (tBHQ)
OT  - thromboxane
COIS- The authors declare no conflict of interest.
EDAT- 2022/05/29 06:00
MHDA- 2022/05/29 06:01
PMCR- 2022/04/26
CRDT- 2022/05/28 01:02
PHST- 2022/03/28 00:00 [received]
PHST- 2022/04/15 00:00 [revised]
PHST- 2022/04/19 00:00 [accepted]
PHST- 2022/05/28 01:02 [entrez]
PHST- 2022/05/29 06:00 [pubmed]
PHST- 2022/05/29 06:01 [medline]
PHST- 2022/04/26 00:00 [pmc-release]
AID - antiox11050845 [pii]
AID - antioxidants-11-00845 [pii]
AID - 10.3390/antiox11050845 [doi]
PST - epublish
SO  - Antioxidants (Basel). 2022 Apr 26;11(5):845. doi: 10.3390/antiox11050845.