钙通道阻滞剂对甲亢性高血压大鼠胸主动脉舒张反应的影响  

Vasorelaxant effects of calcium channel blockers on isolated thoracic aortic rings from thyroxine-induced hypertensive rats

作　　者：金松南[1] 金景玉[2] 苏延友[1] 文今福[3] 

机构地区：[1]泰山医学院药学院药物研究所,山东泰安271000 [2]青岛大学医学院药理学教研室,山东青岛266021 [3]泰山医学院动脉粥样硬化研究所,山东泰安271000

出　　处：《中国药理学通报》2009年第12期1615-1618,共4页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No30570669;30971080);山东省教育厅资助项目(NoJ08LG12)

摘　　要：目的探讨T型和L型钙通道阻滞剂对甲亢性高血压大鼠离体胸主动脉舒张反应的影响。方法大鼠皮下每天注射甲状腺素(T4)0.5mg.kg-1的剂量或等体积的生理盐水维持16d,制备甲亢性高血压大鼠模型组和对照组。采用甲亢性高血压大鼠模型组和对照组的大鼠离体胸主动脉血管环标本,观察T型钙通道阻滞剂mibefradil(mibe)和L型钙通道阻滞剂diltiazem(dilt)对两组大鼠胸主动脉血管环舒张反应的影响。结果与对照组相比,甲亢性高血压大鼠体重明显下降而心率和收缩压明显升高;胸主动脉血管细胞外膜明显增厚,平滑肌细胞核变大并排列不规则。甲亢性高血压疾病时,T型和L型钙通道阻滞剂对胸主动脉的舒张作用明显增强。结论甲亢性高血压病理状态下,胸主动脉T型和L型钙通道的功能增强,可能成为治疗甲亢性高血压的药物靶点。Aim To investigate the effects of T-and L-type calcium channel blockers on isolated thoracic aorta from thyroxine-induced hypertensive rats.Methods Hyperthyroidism was induced by administering L-thyroxine （T4,0.5 mg·kg^-1sc） daily for 16 days.Sham-treated euthyroid control rats were only received vehicle saline for 16 days.Experiments were performed in isolated thoracic aorta rings from euthyroid and hyperthyroid rats.Mibefradil and diltiazem were used to inhibit T-and L-type calcium channels,respectively.Results Thyroid hormone excess for 16 days induced characteristic changes in body weight,heart rate and systolic blood pressure in rats.The body weight was significantly decreased,heart rate and systolic blood pressure were increased in T4-treated rats.Thoracic aorta morphology was altered in T4-treated rats.The thickness of adventitia was increased with hypertrophy and hyperplasia of the smooth musle cells in T4-treated rats.Vasorelaxant effect of T-and L-type calcium channel blockers were accentuated in aortic rings from T4-treated rats.Conclusion These data suggest that T-and L-type calcium channels are functionally upregulated in isolated thoracic aorta from hyperthyroid rats and they,may be a therapeutic target in thyroxine-induced hypertension.

关 键 词：T型钙通道 L型钙通道 甲亢 高血压 胸主动脉 舒张 

分 类 号：R-332[医药卫生] R322.121