BRL 37344急性用药对心力衰竭大鼠血流动力学和β肾上腺素受体表达的影响(英文)  

Effects of acute injection of BRL 37344 on hemodynamics and β-adrenoreceptors expression in myocardium of rats with heart failure

作　　者：孔一慧[1] 杨宝峰[2] 李为民[1] 杨树森[1] 田颖[1] 薛竞宜[1] 李宝馨[2] 

机构地区：[1]哈尔滨医科大学第一临床医学院心内科,黑龙江哈尔滨150001 [2]哈尔滨医科大学药学院,黑龙江哈尔滨150001

出　　处：《中国药理学与毒理学杂志》2006年第1期33-38,共6页Chinese Journal of Pharmacology and Toxicology

基　　金：黑龙江省教育厅资助项目(10551171);黑龙江省卫生厅资助项目(2002-036)~~

摘　　要：目的观察心力衰竭大鼠急性给予β3肾上腺素受体（β3-AR）激动剂BRL37344是否与慢性给药一样，使β3-AR表达进一步增加，心脏功能进一步恶化。方法大鼠SC异丙肾上腺素（Iso，340mg·kg^-1，2次，间隔24h）制备心衰模型。8周后静脉给予BRL373440．4nmol·kg^-1·min^-1，10min，测定给药后0，10，30min，1，2，3h，1，2和7d的血流动力学变化；逆转录聚合酶链反应方法测定0，1，2和7d的心肌组织β—AR mRNA水平。结果与Iso模型组相比，Iso＋BRL组注射BRL 37344后1～3h心率、＋dp／dtmax和左室收缩末压明显增加，左室舒张末压明显降低，之后恢复至注射BRL 37344前水平。与正常对照组相比，BRL组注射BRL37344后β1-β2-和β3-AR水平变化不明显，Iso组β1-ARmRNA水平明显降低，β3-ARmRNA水平明显上升。Iso＋BRL组注射BRL37344后d2起，β1-AR mRNA水平较Iso组进一步降低，β3-AR mRNA进一步上升，d7时变化更明显。结论BRL37344急性用药对衰竭心脏血流动力学有短暂的改善作用，但与慢性给药同样使衰竭心脏β1-AR mRNA水平下降和β3-AR mRNA水平上升，这有可能导致心脏功能的恶化。AIM To observe whether acute stimulation of BRL 37344, a β3-adrenergic receptor （β3-AR） ag- onist, has the same effects of exacerbating hemodynamits and increasing in β3-AR expression on rats with failing heart as chronic administration. METHODS Rats received two doses of isoprenaline （Iso, 340 mg· kg^- 1, sc, with a 24-h interval） to prepare heart failure model. After 8 weeks, rats were given iv BRL 37344 0.4 nmol· kg^-1· min^-1 for 10 rain. Hemodynamics were measured at 0, 10, 30 min, 1,2, 3 h, 1, 2 and 7 d after BRL 37344. Levels of β-AR mRNA in myocardium were measured at 0, 1, 2 and 7 d after BRL 37344 by reverse transcription-polymerase chain reaction. RESULTS Compared with lso group, heart rate, left ventrieular end systolic pressure and ＋ dp/dtmax were significantly higher, and left ventricular end diastolic pressure was significantly lower during 1-3 h after BRL 37344 injection in Iso ＋ BRL group. Then, they were restored to the same level as that prior to BRL 37344 injection. Compared with normal control, the levels of β1-, β2- and β3-AR mRNA displayed no significant change in BRL group; the level of β1-AR mRNA was lower and the level of β3-AR mRNA was higher in Iso group. In Iso ＋ BRL group, much more lower β1-AR mRNA level and much higher β3-AR mRNA lcvel were shown on d 2 and d 7 than Iso group. CONCLUSION Acute administration of β3- AR agonist has a shorter improved hemodynamics. But it caused the same result as chronic administration in reduction of β1-AR mRNA and increment of β3-AR mRNA in failure hearts, which may aggravate the car- diac functions.

关 键 词：受体 肾上腺素 B 基因表达 心力衰竭 BRL 37344 

分 类 号：R96[医药卫生—药理学]