Role of xanthine oxidase in conduit artery endothelial dysfunction in cigarette smokers

doi:10.1016/j.amjcard.2003.11.046

The American Journal of Cardiology

Volume 93, Issue 5, 1 March 2004, Pages 664-668

https://doi.org/10.1016/j.amjcard.2003.11.046 Get rights and content

Abstract

Xanthine oxidase contributes to oxidant stress and has been proposed as a risk factor for endothelial dysfunction. We studied the role of xanthine oxidase in conduit artery endothelial dysfunction in 12 smokers and 12 controls. Conduit artery vasodilation was impaired in smokers (4.3%) compared with controls (7.9%) (p = 0.006) and improved with xanthine oxidase inhibition in smokers (9.2%, p <0.001).

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Xanthine oxidase inhibitors have been shown to improve endothelial function and arterial stiffness in the systemic circulation [163–167]. They have also been shown to reduce endothelial dysfunction induced by smoking and obstructive sleep apnoea [168–170] – a condition similar to COPD in its effects of intermittent hypoxia [171]. Additionally allopurinol inhibits hypoxia induced pulmonary vasoconstriction, pulmonary hypertension, endothelial dysfunction and vascular remodelling in hypoxic animal models of pulmonary hypertension [172–176].
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Cell pre-treatment with allopurinol or febuxostat demonstrated that DNA damage was dependent on XOR activity, thus establishing a role for XOR in cigarette smoking-induced endothelial cell injury [33]. Allopurinol reversed the alteration of vessel resistance induced by smoking in subjects with no other risk factors for atherosclerosis, suggesting that XOR contributes to endothelial dysfunction caused by cigarette smoking [34,35]. Increased superoxide production by endothelial cells has been reported in diet-induced hypercholesterolemic rabbits, possibly due to XOR activity [36].
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Brief reportRole of xanthine oxidase in conduit artery endothelial dysfunction in cigarette smokers

Abstract

J Biol Chem

J Biol Chem

J Biol Chem

Cigarette smoking is associated with dose-related and potentially reversible impairment of endothelium-dependent dilation in healthy young adults

Circulation

Antioxidant vitamin C improves endothelial dysfunction in chronic smokers

Circulation

Endothelium-dependent vasodilation in the brachial artery is impaired in smokerseffect of vitamin C

Am J Physiol

Xanthine oxidase inhibition reverses endothelial dysfunction in heavy smokers

Circulation

Xanthine oxidase inhibition with oxypurinol improves endothelial vasodilator function in hypercholesterolemic but not in hypertensive patients

Hypertension

Allopurinol normalizes endothelial dysfunction in type 2 diabetics with mild hypertension

Hypertension

Allopurinol improves endothelial dysfunction in chronic heart failure

Circulation

Brief report
Role of xanthine oxidase in conduit artery endothelial dysfunction in cigarette smokers