Endothelial Function and Oxidant Stress

David G. Harrison

Clinical Cardiology · 1997 · 305 citations · 44 references

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TL;DR

Endothelial and vascular smooth muscle cells produce reactive oxygen species, and their production rises markedly in atherosclerosis and hypertension. Superoxide anion reduces nitric oxide levels through rapid radical reactions, and the NADH‑dependent oxidase that generates superoxide is upregulated by angiotensin II and chronic nitroglycerin exposure. Elevated superoxide impairs endothelial vasomotion, with the NADH‑dependent oxidase identified as the main source, and angiotensin II–induced oxidant changes may link hypertension to atherosclerosis.

Abstract

Both endothelial cells and vascular smooth muscle cells are capable of producing reactive oxygen species from a variety of enzymatic sources. In disease states such as atherosclerosis and hypertension, vascular production of these reactive oxygen metabolites can increase substantially. Increases in the production of superoxide anion can lead to decreases in ambient levels of nitric oxide via a facile radical/radical reaction that occurs more rapidly than the reaction of superoxide anion with superoxide dismutase. This phenomenon alters endothelial regulation of vasomotion in a variety of disease conditions. Recent evidence suggests that the major source of vascular superoxide ion and hydrogen peroxide is a membrane-bound, reduced nicotinamide-adenine dinucleotide (NADH)-dependent oxidase. The activity of this enzyme system is regulated by angiotensin II and is elevated following prolonged exposure to nitroglycerin. Alterations of vascular oxidant state caused by angiotensin II may contribute substantially to vascular pathology and may also provide a link between hypertension and atherosclerosis.

References

44