Allopurinol improves endothelial function in NIDDM, but has no effect in aged-matched and young non-diabetic controls

There is evidence that anti-oxidant therapies improve endothelial function (EF) in diabetic patients. Xanthine oxidase is a key free radical enzyme generating system and therefore allopurinol, a xanthine oxidase inhibitor may produce a similar beneficial effects on EF. Methods: We examined 34 patients (11 patients with NIDDM, mean age (MA)=65 years; 12 similar aged controls, MA=59 years and 11 young healthy volunteers, MA=25 years) treated with 300mg of allopurinol (1 month) in a randomised, placebo controlled, double-blind, cross-over study. EF was assessed by bi-lateral forearm venous occlusion plethysmography using endothelial dependent (acetyl choline) and endothelial independent vasodilators (sodium nitroprusside). Results: Forearm blood flow (FBF) response to acetyl choline showed a significant increase with allopurinol therapy in the NIDDM subgroup (2.63 vs. 2.16 ml/100mls/min; allopurinol vs. placebo p=0.01; 95% CI 0.11,0.83) but no improvement with nitroprusside. There was a significant reduction in malonyldiadlehyde (MDA) (0.30 vs. 0.34 μM/l; allopurinol vs. placebo p=0.02). There was no difference in HbA1c, cholesterol or blood pressure between the study days. There was no significant difference between either endothelial dependent or independent response in either the young or old normal subgroups. These results indicate for the first time that the allopurinol improves EF but only in NIDDM. Allopurinol may decrease free radical generation, in particular superoxide, increasing nitric oxide bioavailability.