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(Stroke. 2005;36:160.)
© 2005 American Heart Association, Inc.

Research Reports

Editorial Comment: eNOS: Can We Exploit the Good?

Frank M. Faraci, PhD

Departments of Internal Medicine and Pharmacology, Cardiovascular Center, University of Iowa Carver College of Medicine, Iowa City, Iowa

An extract of the first 250 words of the full text is provided, because this article has no abstract.

One of the major functions of vascular endothelium is to regulate tone of underlying smooth muscle. This function is mediated in large part by release of diverse endothelium-derived relaxing factors (EDRFs).^1,2 A major EDRF that regulates both cerebral vascular function and structure is nitric oxide (NO) produced by the endothelial isoform of NO synthase (eNOS).^1,3 Most studies indicate that NO is the predominant EDRF in the cerebral circulation.¹ Although dozens of studies in animal models support this view, it is important to recall that NO is also a major EDRF in both large arteries and microvessels in the human brain.^1,4

In the present study by Sorenson et al,⁵ the investigators examined effects of gene transfer of a mutant form of eNOS (S1179DeNOS) that is constitutively active (ie, active in the absence of agonist induced stimulation) on vascular function in human pial arteries obtained at the time of surgery. Because eNOS has many beneficial effects within the vessel wall, it was of interest to examine effects of expression of S1179DeNOS on vascular function.

Expression of S1179DeNOS increased basal levels of cyclic GMP, a key second messenger in relation to NO-mediated signaling, and reduced responses to an endothelium-dependent agonist and an NO donor. Reduced responses to NO in vessels that express S1179DeNOS probably reflects a compensatory response within vascular muscle because of increase basal levels of NO.

Reduced responses to NO in these experiments did not appear to be mediated by oxidative stress as a scavenger of the free radical superoxide had . . . [Full Text of this Article]