Allopurinol and nitric oxide activity in the cerebral circulation of those with diabetes: a randomized trial

Diabetes Care. 2009 Jan;32(1):135-7. doi: 10.2337/dc08-1179. Epub 2008 Oct 22.

Abstract

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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allopurinol / blood
  • Allopurinol / therapeutic use*
  • Carotid Arteries / drug effects
  • Carotid Arteries / physiopathology*
  • Cerebrovascular Circulation / physiology*
  • Cross-Over Studies
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetic Angiopathies / prevention & control
  • Double-Blind Method
  • Humans
  • Infusions, Intravenous
  • Male
  • Nitric Oxide / blood*
  • Placebos
  • Stroke / prevention & control
  • omega-N-Methylarginine / administration & dosage
  • omega-N-Methylarginine / therapeutic use*

Substances

  • Placebos
  • omega-N-Methylarginine
  • Nitric Oxide
  • Allopurinol

Associated data

  • ISRCTN/ISRCTN68849312