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J Biol Chem. 2002 Dec 13;277(50):48803-7. Epub 2002 Oct 2.

Reduction of blood pressure, plasma cholesterol, and atherosclerosis by elevated endothelial nitric oxide.

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  • 1Department of Cell Biology and Genetics, Thoraxcenter, Erasmus Laboratory Animal Science Center, Erasmus Medical Center, P. O. Box 1738, 3000DR Rotterdam, The Netherlands.


In the vascular system, nitric oxide is generated by endothelial NO synthase (eNOS). NO has pleiotropic effects, most of which are believed to be atheroprotective. Therefore, it has been argued that patients suffering from cardiovascular disease could benefit from an increase in eNOS activity. However, increased NO production can cause oxidative damage, cell toxicity, and apoptosis and hence could be atherogenic rather than beneficial. To study the in vivo effects of increased eNOS activity, we created transgenic mice overexpressing human eNOS. Aortic blood pressure was approximately 20 mm Hg lower in the transgenic mice compared with control mice because of lower systemic vascular resistance. The effects of eNOS overexpression on diet-induced atherosclerosis were studied in apolipoprotein E-deficient mice. Elevation of eNOS activity decreased blood pressure ( approximately 20 mm Hg) and plasma levels of cholesterol ( approximately 17%), resulting in a reduction in atherosclerotic lesions by 40%. We conclude that an increase in eNOS activity is beneficial and provides protection against atherosclerosis.

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