(Circulation. 1996;94:240-243.)
© 1996 American Heart Association, Inc.
Articles |
Reversing Endothelial Dysfunction With ACE Inhibitors
A New TREND?
the Division of Cardiology, Emory University School of Medicine (S.R., D.G.H.), and Veterans Administration Hospital (D.G.H.), Atlanta, Ga.
Correspondence to David G. Harrison, Professor of Medicine, Cardiology Division, Emory University School of Medicine, Atlanta, GA 30322. (Circulation. 1996,94:240-243.)
Key Words: Editorials • endothelium-derived factors • vasoconstriction • vasodilation
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Introduction |
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During the past 15 years, it has become apparent that the vascular endothelium plays a crucial role in modulating vasomotor tone. The endothelium accomplishes this by synthesizing and releasing several vasoactive substances, including prostacyclin, adenine nucleotides, kinins, NO·, an as-yet-unidentified hyperpolarizing factor, and vasoconstrictor substances such as endothelin, vasoconstrictor prostanoids such as PGH2, and the superoxide anion (·O2-).1 2 3 Among the best characterized and likely the most important of these is NO·, which was previously known as EDRF.4 NO is produced by the endothelium when a variety of neurohumoral, paracrine, and pharmacological stimuli act on endothelial cell receptors to increase intracellular calcium, which ultimately activates endothelial cell NO synthase. This enzyme catalyzes the complex oxidation of one of the guanidino nitrogens of arginine to NO·.5 There is substantial evidence that NO· may be transported attached to other molecules, such as nitrosothiols, both between cells and in the plasma.6 7 Vascular smooth muscle cells possess receptors to many of the same agonists that activate NO· release from the endothelium. Thus, the ultimate effect of any given stimulus for NO· release is a balance between the vasodilator effect of NO· versus the direct vasoconstrictive effect of the stimulus on the vascular smooth muscle.
A clinically important aspect of this important role of the endothelium is that it is impaired in a variety of diseases and conditions. These include hypertension, hypercholesterolemia, diabetes, transplant atherosclerosis, congestive heart failure, and cigarette smoking. NO· has a variety of beneficial, potentially antiatherogenic effects in the vessel wall.
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