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Allopurinol Prevents Nitroglycerin-induced Tolerance in Rat Thoracic Aorta

Azarmi, Yadollah PhD*,†; Babaei, Hossein PhD, PharmD*,†; Alizadeh, Fatemeh PharmD; Gharebageri, Afsaneh PharmD*; Fouladi, Daniel F. MD*; Nikkhah, Elhameh MSc*

Journal of Cardiovascular Pharmacology: February 2014 - Volume 63 - Issue 2 - p 113–119
doi: 10.1097/FJC.0000000000000029
Original Article

Abstract: Xanthine oxidase is an important source of reactive oxygen species; so, it may play a role in the pathogenesis of endothelium dysfunction and its consequences. Allopurinol, a purine analog, is a famous xanthine oxidase inhibitor. This study aimed to investigate possible effects of allopurinol on nitroglycerin tolerance, vasoconstriction, and vasorelaxation in rat aortic ring. Using thoracic aortic rings obtained from male Wistar rats, the effect of allopurinol was examined on nitroglycerin-induced tolerance. In addition, changes of vasoconstriction (by using KCl and phenylephrine) and vasorelaxation (by using carbachol, sodium nitroprusside, and nitroglycerin) were also measured and compared between tissues treated with and without allopurinol. All 3 concentrations of allopurinol (50, 100, and 150 μM) significantly acted against the development of nitroglycerin-induced tolerance in comparison with controls. In terms of vasoconstriction and vasorelaxation, the effect of allopurinol was significant only on carbachol-induced (endothelium related) vasorelaxation in a dose-dependent manner. In conclusion, although allopurinol had no significant effect on the contractile response of the aorta, in accord with the previous data, it significantly intensified endothelium-dependent vasodilation. The inhibitory effect of allopurinol against the development of nitrate-induced tolerance may suggest its clinical benefit and is worth to be studied more extensively.

*Drug Applied Research Center; and

School of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.

Reprints: Hossein Babaei, PhD, PharmD, Drug Applied Research Center, Tabriz University of Medical Sciences, Research and Development Complex, Daneshgah St, Tabriz, Iran 51656-65811 (e-mail:

The authors report no funding or conflicts of interest.

Received May 17, 2013

Accepted October 01, 2013

© 2014 by Lippincott Williams & Wilkins.