Allopurinol and nitric oxide activity in the cerebral circulation of those with diabetes

Dawson, J., Quinn, T.J., Harrow, C., Lees, K.R., Weir, C., Cleland, S. and Walters, M. (2009) Allopurinol and nitric oxide activity in the cerebral circulation of those with diabetes. Diabetes Care, 32(1), pp. 135-137. (doi:10.2337/dc08-1179)

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Abstract

<br>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.</br> <br>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.</br> <br>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]).</br> <br>CONCLUSIONS—Xanthine oxidase inhibition with allopurinol appears to improve cerebral NO bioavailability, as evidenced by a greater response to infusion of l-NMMA. Type 2 diabetes conveys an increased risk of stroke (1,2), perhaps because of impaired cerebrovascular basal nitric oxide (NO) bioavailability—a hypothesis suggested by impaired response to infusion of the endothelial NO synthase inhibitor NG-monomethyl-l-arginine (l-NMMA) (3). We performed a randomized, double-blind, placebo-controlled crossover study to test whether this response is improved following a course of the xanthine oxidase inhibitor allopurinol.</br>

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Lees, Professor Kennedy and Cleland, Dr Stephen and Weir, Christopher and Quinn, Dr Terence and Dawson, Professor Jesse and Walters, Professor Matthew
Authors: Dawson, J., Quinn, T.J., Harrow, C., Lees, K.R., Weir, C., Cleland, S., and Walters, M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Robertson Centre
Journal Name:Diabetes Care
Publisher:American Diabetes Association
ISSN:0149-5992
ISSN (Online):1935-5548
Published Online:22 October 2008
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