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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:719.)
© 2001 American Heart Association, Inc.

Editorials

NO or H₂O₂ for Endothelium-Dependent Vasorelaxation

Tetrahydrobiopterin Makes the Difference

Victor W. M. van Hinsbergh

From the Gaubius Laboratory, Leiden, and the Department of Physiology, Institute for Cardiovascular Research, Vrije Universiteit Medical Center, Amsterdam, the Netherlands.

Correspondence to Dr Victor W.M. van Hinsbergh, Gaubius Laboratory TNO-PG, Zernikedreef 9, 2301 CE Leiden, Netherlands. E-mail vwm.vanhinsbergh@pg.tno.nl

Key Words: nitric oxide synthase • hydrogen peroxide • superoxide anion • catalase GTP cyclohydrolase I

Rapid adaptation of the diameter of blood vessels is an important regulatory mechanism for regulating blood pressure and for limiting tissue damage resulting from wounding or ischemia. Endothelial cells contribute to vasoregulation by the production of potent vasodilators. Loss or reduction of endothelium-dependent vasorelaxation is one of the reflections of endothelial dysfunction, an early hallmark in the development of atherosclerosis. Studies in patients have pointed to an impairment of endothelium-dependent vasodilation in a number of conditions that also increase the risk of developing cardiovascular complications, including hypercholesterolemia, hypertension, and diabetes.^{1 2 3 4} This impairment is due to a reduced availability of NO, a major endothelium-dependent vasorelaxing factor.^{5 6} Several studies have indicated that supplementation of tetrahydrobiopterin (H₄B), a cofactor of the endothelial NO synthase, can improve endothelium-dependent arterial vasoregulation in atherosclerotic and diabetic patients.^{7 8 9 10} In the April issue of Arteriosclerosis, Thrombosis, and Vascular Biology, Cosentino et al¹¹ use transgenic mice to achieve a 60% reduction of arterial H₄B, and they demonstrate that this reduction is accompanied by a marked decrease of NO production while H₂O₂ production is increased.

Endothelial cells produce NO from L-arginine by NO synthase-3 (NOS-3), also called constitutive or endothelial NOS. The enzyme is constitutively present in endothelial cells and becomes active by interaction with the Ca²⁺/calmodulin complex, which is transiently generated after exposure of the endothelial cell to vasoactive agents, or by phosphorylation at serine 1117 by the serine/threonine protein kinase Akt.^{12 13} Arterial shear forces and estrogen are among the factors that can . . . [Full Text of this Article]

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