Allopurinol and Nitric Oxide Activity in the Cerebral Circulation of Those With Diabetes: A randomized trial

OBJECTIVE—Type 2 diabetes increases risk of stroke, perhaps because of impaired cerebrovascular basal nitric oxide (NO) activity. We investigated whether this activity is improved by a 2-week course of the xanthine oxidase inhibitor allopurinol. RESEARCH DESIGN AND METHODS—We performed a randomized, double-blind, placebo-controlled crossover study. We measured the response to infusion of NG-monomethyl-L-arginine (l-NMMA) in males with type 2 diabetes before and after allopurinol or placebo. The primary end point was the change in internal carotid artery flow following l-NMMA infusion, expressed as the area under the flow-per-time curve. RESULTS—We enrolled 14 participants. Allopurinol improved responses to l-NMMA when compared with responses associated with placebo (P = 0.032; median reduction in internal carotid artery flow following l-NMMA of 3,144 ml [95% CI 375–7,143]). CONCLUSIONS—Xanthine oxidase inhibition with allopurinol appears to improve cerebral NO bioavailability, as evidenced by a greater response to infusion of l-NMMA.