中国药理学与毒理学杂志Issue(2):208-212,5.DOI:10.3867/j.issn.1000-3002.2015.02.004
多沙唑嗪和美托洛尔对腹主动脉缩窄致高血压大鼠血管重塑的影响
Effect of doxazosin and metoprolol on vascuIar remodeling in rats with hypertension induced by abdominal aorta coarctation
摘要
Abstract
OBJECTIVE To investigate the effect of doxazosin(DOX) and metoprolol( MET) on vascular remodeling in rats with abdominal aorta coarctation (AAC). METHODS An animal model was established by AAC. Two weeks later, the rats were treated with DOX (10 mg.kg-1 per day) or MET (20 mg.kg-1 per day) for six weeks. Blood pressure was measured using carotid artery intubation with a MP150 polygraph. The media thickness, wall cross-sectional area and thickness / internal diameter ratio were calculated by morphometry. Vascular fibrosis was evaluated by Masson′s trichrome staining. The collagen and fibronectin expression in vascules was measured by Western blotting. RESULTS Compared with the sham group 〔(17.6±0.5)kPa〕, the mean arterial blood pressure in the model group〔(23.3±0.7)kPa〕 was significantly increased(P<0.05), but was lowered by DOX 〔(20.5±0.7)kPa〕 and MET 〔(19.0±0.4) kPa〕 (P<0.05). Moreover, HE staining showed that tunica media thickness, artery vessel area and thickness / inner diameter in the model group were increased by 39.5%, 46.4% and 27.0%(P<0.05), respectively. The tunica media thickness was decreased by 16.0% and 26.1%( P<0.05), respectively, the artery vessel area by 22.8% and 26.1%(P<0.05), respectively, and the thick-ness / inner diameter by 17.0% and 26.0%( P<0.05) when the rats were treated with DOX and MET. Masson staining showed that the collagen accumulation in vascules increased, suggesting that AAC induced fibrosis. Meanwhile, vascular fibrosis induced by AAC was also reduced by MET or DOX. Western blotting also proved that the increase of collagen and fibronectin induced by AAC could be attenuated by DOX and MET(P<0.05). CONCLUSION DOX and MET are effective in suppressing the role of norepi-nephrine in vassels, which can attenuate AAC-induced vassels remodeling by preventing the binding between norepinephrine and adrenoceptors.关键词
血管重塑/高血压/多沙唑嗪/美托洛尔Key words
vascular remodeling/hypertension/doxazosin/metroprolol分类
医药卫生引用本文复制引用
黄立双,姚林,钱令嘉,刘伟丽,弓景波,杲修杰,赵云,马婧,谢方,张涛,田凯琦..多沙唑嗪和美托洛尔对腹主动脉缩窄致高血压大鼠血管重塑的影响[J].中国药理学与毒理学杂志,2015,(2):208-212,5.基金项目
国家重点基础研究发展规划(2011CB505106)天津市自然科学重点基金(10JCZDJC19300)@@@@The project supported by National Program on Key Basic Research Project of China (2011CB505106) and Tianjin Municipal Natural Science Fund(10JCZD19300) (2011CB505106)