The Effect of Chronic Hyperthyroidism and Restored Euthyroid State by Methimazole Therapy in Rat Small Mesenteric Arteries Publisher Pubmed



Khorshidibehzadi M¹ ; Alimoradi H² ; Haghjoojavanmard S¹ ; Reza Sharifi M³ ; Rahimi N⁴ ; Dehpour AR⁵ Show Affiliations
Source: European Journal of Pharmacology Published:2013

Abstract

Not much has been reported about the effects of hyperthyroidism and its correction on resistance vessels, and just two inconsistent studies have investigated the impacts of restored euthyroidism on vascular reactivity. In this regard, we designed the current study to evaluate the vascular reactivity of the mesenteric arteries of hyperthyroid and restore euthyroid rats. Hyperthyroidism was induced by administration of triiodothyronine (T 3; 300 μg/kg, i.p., for 12 weeks in T3 group). Euthyroidism was restored by administration of T3 for 8 weeks and then T3+Methimazole (0.003% in drinking water) for 4 weeks (T 3+MMI group). According to the McGregor method, vascular relaxation and contractility response were measured in response to acetylcholine or phenylephrine respectively. We found that maximal contractility response (E max) to phenylephrine in the T3 group was significantly decreased (P<0.001), and Emax to acetylcholine was significantly increased compared with the saline group (P<0.05). When NG-nitro- L-arginine methyl ester (L-NAME, 3×10-4 M) was used, E max to acetylcholine in the T3 group was still higher than the saline group (P<0.05). However, decrease in maximal response of the T3 group was significantly greater than the saline group (P<0.01). We also showed that when euthyroidism is restored by methimazole therapy, enhanced acetylcholine-induced vasorelaxation and impaired contractility response to phenylephrine were normalized, as there was no significant difference in Emax of the T3+MMI group versus the saline group (P>0.05). In conclusion, synthesis of both nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) in mesenteric arteries significantly increased as a consequence of hyperthyroidism, and this abnormal vascular reactivity is corrected by methimazole therapy. © 2012 Elsevier B.V. All rights reserved.