PMID- 32363908
OWN - NLM
STAT- MEDLINE
DCOM- 20211129
LR  - 20231213
IS  - 1557-7716 (Electronic)
IS  - 1523-0864 (Print)
IS  - 1523-0864 (Linking)
VI  - 34
IP  - 9
DP  - 2021 Mar 20
TI  - Oxidative Stress, GTPCH1, and Endothelial Nitric Oxide Synthase Uncoupling in 
      Hypertension.
PG  - 750-764
LID - 10.1089/ars.2020.8112 [doi]
AB  - Significance: Hypertension has major health consequences, which is associated 
      with endothelial dysfunction. Endothelial nitric oxide synthase (eNOS)-produced 
      nitric oxide (NO) signaling in the vasculature plays an important role in 
      maintaining vascular homeostasis. Considering the importance of NO system, this 
      review aims to provide a brief overview of the biochemistry of members of NO 
      signaling, including GTPCH1 [guanosine 5'-triphosphate (GTP) cyclohydrolase 1], 
      tetrahydrobiopterin (BH(4)), and eNOS. Recent Advances: Being NO signaling 
      activators and regulators of eNOS signaling, BH(4) treatment is getting 
      widespread attention either as potential therapeutic agents or as preventive 
      agents. Recent clinical trials also support that BH(4) treatment could be 
      considered a promising therapeutic in hypertension. Critical Issues: Under 
      conditions of BH(4) depletion, eNOS-generated superoxides trigger pathological 
      events. Abnormalities in NO availability and BH(4) deficiency lead to disturbed 
      redox regulation causing pathological events. This disturbed signaling influences 
      the development of systemic hypertension as well as pulmonary hypertension. 
      Future Directions: Considering the importance of BH(4) and NO to improve the 
      translational significance, it is essential to continue research on this field to 
      manipulate BH(4) to increase the efficacy for treating hypertension. Thus, this 
      review also examines the current state of knowledge on the effects of eNOS 
      activators on preclinical models and humans to utilize this information for 
      potential therapy.
FAU - Wu, Yin
AU  - Wu Y
AD  - Center for Molecular and Translational Medicine, Georgia State University, 
      Atlanta, Georgia, USA.
FAU - Ding, Ye
AU  - Ding Y
AD  - Center for Molecular and Translational Medicine, Georgia State University, 
      Atlanta, Georgia, USA.
FAU - Ramprasath, Tharmarajan
AU  - Ramprasath T
AD  - Center for Molecular and Translational Medicine, Georgia State University, 
      Atlanta, Georgia, USA.
FAU - Zou, Ming-Hui
AU  - Zou MH
AD  - Center for Molecular and Translational Medicine, Georgia State University, 
      Atlanta, Georgia, USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20200527
PL  - United States
TA  - Antioxid Redox Signal
JT  - Antioxidants & redox signaling
JID - 100888899
RN  - 0 (Biopterins)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
RN  - EC 3.5.4.16 (GCH1 protein, human)
RN  - EC 3.5.4.16 (GTP Cyclohydrolase)
RN  - EGX657432I (sapropterin)
SB  - IM
MH  - Biopterins/analogs & derivatives/metabolism
MH  - GTP Cyclohydrolase/*genetics
MH  - Humans
MH  - Hypertension/*genetics/metabolism/pathology
MH  - Nitric Oxide/genetics/metabolism
MH  - Nitric Oxide Synthase Type III/*genetics/metabolism
MH  - Oxidative Stress/*genetics
MH  - Signal Transduction/genetics
PMC - PMC7910417
OTO - NOTNLM
OT  - GTPCH1
OT  - eNOS uncoupling
OT  - endothelial nitric oxide synthase
OT  - hypertension
EDAT- 2020/05/05 06:00
MHDA- 2021/11/30 06:00
PMCR- 2022/03/20
CRDT- 2020/05/05 06:00
PHST- 2020/05/05 06:00 [pubmed]
PHST- 2021/11/30 06:00 [medline]
PHST- 2020/05/05 06:00 [entrez]
PHST- 2022/03/20 00:00 [pmc-release]
AID - 10.1089/ars.2020.8112 [pii]
AID - 10.1089/ars.2020.8112 [doi]
PST - ppublish
SO  - Antioxid Redox Signal. 2021 Mar 20;34(9):750-764. doi: 10.1089/ars.2020.8112. 
      Epub 2020 May 27.