Allopurinol and Nitric Oxide Activity in the Cerebral Circulation of Those With Diabetes
A randomized trial
- Jesse Dawson, MRCP1,
- Terry Quinn, MRCP1,
- Craig Harrow, MRCP1,
- Kennedy R. Lees, MD, FRCP1,
- Christopher J. Weir, PHD2,
- Stephen J. Cleland, PHD, FRCP3 and
- Matthew R. Walters, MD, FRCP1
- 1Acute Stroke Unit, Division of Cardiovascular and Medical Sciences, University of Glasgow, Western Infirmary, Glasgow, U.K.
- 2Robertson Centre for Biostatistics, University of Glasgow, Glasgow, U.K.
- 3Stobhill Hospital, Glasgow, U.K.
- Corresponding author: Jesse Dawson, j.dawson{at}clinmed.gla.ac.uk
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.
Footnotes
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Published ahead of print at http://care.diabetesjournals.org on 22 October 2008.
Clinical trial reg. no. ISRCTN68849312, controlled-trials.com/isrctn.
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- Accepted October 15, 2008.
- Received July 14, 2008.
- DIABETES CARE
