Oxidation of tetrahydrobiopterin leads to uncoupling of endothelial cell nitric oxide synthase in hypertension.

By U. Landmesser, S. Dikalov, S. Price, Louise A. McCann, T. Fukai, S. Holland, W. Mitch, D. Harrison. Journal of Clinical Investigation, 2003

1,686 citations recorded by the source corpus.

Subfields: Biochemistry, Cardiology and Cardiovascular Medicine, Physiology

View Paper: https://www.semanticscholar.org/paper/765ff6f98f03e9092cb5040735452ace03c2a88d

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In Biochemistry

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Citations in the corpus

Redox signaling in hypertension. (2006, background): “Similarly, rats with DOCA salt-induced mineralocorticoid hypertension also show elevated vascular O2 & production that appears to be due to elevated NAD(P)H oxidase activity and may also involve subsequent uncoupling of endothelial NOS [23,40,41].”
Crosstalk between mitochondria and NADPH oxidases (2011, background): “the endothelial NO synthase, it has been found that hypertension is a result of the cascade involving production of ROS from the NADPH oxidases leading to oxidation of tetrahydrobiopterin and uncoupling of eNOS [20].”
Nox proteins in signal transduction (2009, background): “eNOS uncoupling has also been shown to be a direct result of Nox activation [76].”
Endothelial cell superoxide generation: regulation and relevance for cardiovascular pathophysiology. (2004, background): “Furthermore, BH4 itself is highly susceptible to oxidative degradation, and the initial oxidative loss of BH4 in response to increased ROS production by NADPH oxidases has been shown to amplify oxidative stress through the resulting loss of NO production and increased NOS-dependent O2 generation (86”
Methods for detection of reactive metabolites of oxygen and nitrogen: in vitro and in vivo considerations. (2004, methodology): “It has, however, been used to detect superoxide formation in vascular tissue (71).”
Endothelial dysfunction. (2004, background): “The reductase function of eNOS is activated and more ROS are formed, so NO synthase goes from its oxygenase function producing NO to its reductase function producing ROS, with the consequent exaggeration of oxidant excess and deleterious effect on endothelial and vascular function (31).”
Nitric oxide synthases: regulation and function. (2012, background): “…via the ﬂavins FAD and FMN to the haem, where the substrate L -arginine is oxidized to L -citrulline and NO. 99 The reaction product of NO and O 2 2 105,106 and BH 4 levels have been found decreased in many models of cardiovascular disease 107–109,101 and in patients with endothelial dysfunction.”