The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 6 No.
4 • September 2003
Xanthine Oxidase and Endothelial Dysfunction in Heavy Smokers
Xanthine oxidase (XO) is one of the major free radical-producing enzymes (others are NADPH oxidase, myeloperoxidase, and endotoxin). XO, present in high concentrations in endothelial cells of capillaries and sinusoids, can produce superoxide, as well as other oxygen free radicals. The XO-derived superoxide radicals generate hydrogen peroxide, which can then produce hydroxyl radicals. XO activity is increased in ischemia-reperfusion injuries, anoxia, and inflammation.
An interesting, single-blinded, randomized, 2-phase crossover study of endothelial function in heavy smokers was recently reported. The authors hypothesized that xanthine oxidase contributed to endothelial dysfunction (failure of arteries to dilate in response to acetylcholine) in cigarette smokers. They inhibited XO by giving subjects 600 mg of allopurinol. Earlier studies had shown that oxypurinol, an active metabolite of allopurinol, improved resistance vessel endothelial vasodilator function in hypercholesterolemic, but not hypertensive, patients.
The 14 smokers included in this study were chosen to have no other risk factors for atherosclerosis. Blood vessel dilation produced by acetylcholine was significantly less in smokers (254; +57%) than in healthy controls (390; +55%). Allopurinol reversed the endothelial dysfunction in smokers (acetylcholine, 463; +78%) without affecting responses in nonsmokers (401; +80%).
Few if any people reading this newsletter are likely to be smokers, but you may have a friend or relative who smokes and who may find it useful to take allopurinol, a readily available and inexpensive prescription drug. Durk takes 200 mg/day for gout. Allopurinol can cause liver problems in some people, especially at high doses. Uric acid, a potent destroyer of the strong oxidant peroxynitrite, is made by xanthine oxidase, so we do not recommend that you lower your uric acid levels below the normal human range.
- Guthikonda et al. Xanthine oxidase inhibition reverses endothelial dysfunction in heavy smokers. Circulation 107:416-21 (2003).