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Updated: Dec 22, 2025

En Face Detection of Nitric Oxide and Superoxide in Endothelial Layer of Intact Arteries
Published on: February 25, 2016
Oxidative Stress, GTPCH1, and Endothelial Nitric Oxide Synthase Uncoupling in Hypertension
Yin Wu1, Ye Ding1, Tharmarajan Ramprasath1
1Center for Molecular and Translational Medicine, Georgia State University, Atlanta, Georgia, USA.
Abstract:
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 (BH4), and eNOS. Being NO signaling activators and regulators of eNOS signaling, BH4 treatment is getting widespread attention either as potential therapeutic agents or as preventive agents. Recent clinical trials also support that BH4 treatment could be considered a promising therapeutic in hypertension. Under conditions of BH4 depletion, eNOS-generated superoxides trigger pathological events. Abnormalities in NO availability and BH4 deficiency lead to disturbed redox regulation causing pathological events. This disturbed signaling influences the development of systemic hypertension as well as pulmonary hypertension. Considering the importance of BH4 and NO to improve the translational significance, it is essential to continue research on this field to manipulate BH4 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.
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