title: Allopurinol prevents nitroglycerin-induced tolerance in rat thoracic aorta.
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.
authors.affiliation: *Drug Applied Research Center; and †School of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Yadollah
authors.initials: Y
authors.lastname: Azarmi
authors.forename: Hossein
authors.initials: H
authors.lastname: Babaei
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Alizadeh
authors.forename: Afsaneh
authors.initials: A
authors.lastname: Gharebageri
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Fouladi
authors.forename: Elhameh
authors.initials: E
authors.lastname: Nikkhah
mesh_terms: D000493:Allopurinol / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D005996:Nitroglycerin / Q000008:administration & dosage / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors*
chemical_list: D004791:Enzyme Inhibitors; D014665:Vasodilator Agents; D010656:Phenylephrine; D000493:Allopurinol; D014969:Xanthine Oxidase; D005996:Nitroglycerin