慢性心功不全大鼠心脏α_1受体对β受体正性变力效应调节作用的改变  

Altered effects of α_1-adrenoceptor on β-adrenoceptor induced positive inotropic response in the rat with cardiac insufficiency

作　　者：张幼怡[1] 韩启德[1] 田斌[1] 王丽枫 陈明哲[1] 

机构地区：[1]北京医科大学第三医院血管医学研究所

出　　处：《中国病理生理杂志》1995年第6期567-572,共6页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金;国家博土后基金

摘　　要：本文用缩窄腹主动脉和左肾动脉方法复制慢性心功能不全大鼠模型。用放射配体结合实验观察心脏α＿１肾上腺素受体（α＿１－ＡＲ）及其亚型分布的变化，显示在心功能不全大鼠心肌组织上α＿１－ＡＲ的数量及对￣１２５Ｉ－ＢＥ的亲和性与假手术大鼠无显著差别，但α＿１Ａ亚型占α＿１－ＡＲ总数的比例比假手术大鼠明显增高（５１±７％比２２±５％，Ｐ＜０．０１）。离体左心房收缩功能实验结果显示，两组间心肌最大收缩效应无显著差别；当用１０μｍｏｌ／Ｌ酚妥拉明阻断α＿１－ＡＲ时，心功能不全大鼠去甲肾上腺素（ＮＥ）的浓度－收缩效应曲线无显著左移，用１μｍｏｌ／Ｌ苯肾上腺素激动α＿１－ＡＲ时，亦未使异丙肾上腺素浓度－收缩效应曲线右移，用１ｎｍｏｌ／ＬＷＢ４１０１阻断α＿１Ａ亚型时，ＮＥ浓度－收效应曲线不再出现左移，但２０μｍｏｌ／ＬＣＥＣ不可逆阻断α＿１Ｂ亚型后，ＮＥ浓度－收缩效应曲线仍显著右移。结果提示，心功能不全α＿１－ＡＲ及α＿１Ａ亚型对β－ＡＲ介导的正性变力效应的抑制作用消失，而α＿１Ｂ亚型对β－ＡＲ介导的正性变力效应的增强作用仍存在。The distribution of α_1-adrenoceptor(α_1-AR)subtypes and the effects ofactivation of α_1-AR on β-adrenoceptor(β-AR) mediated positive inotropic response werestudied.The cardiac insufficiency was produced by constriction of both abdominal aorticand renal ateries in rat.Two months post-constriction,the radio ligand binding assaysindicated that neither total α_1-AR density nor the affinity for￣(125)IBE specific binding waschanged in rat with cardiac insufficiency compa red to the sham-operated rats.The per-centage of α_1A-AR in total ￣(125)IBE specific binding sites was higher in rats with cardiacinsufficiency than that in the sham-operated rats(51±+7%vs.22±5%,P<0.01).In thefunctional experiments,the maximal positive inotropic responses to norepinephrine (NE)and isoproterenol(ISO)were also unchanged in the rate with cardiac insufficiency.Theconcentration-response curves(CRC)for NE were not shifted to left any more like inthe sham operated rats in the presence of 10 μmol/L phentolamine which inactivated α_1-AR, and 1 nmol/L WB410 l which inactivated only α_1A-AR did not change the CRC forNE as well.CRC for NE were,however,shifted to the right by the pretreatment of thepreparations with 20μmol/L CEC which inactivated only α_1B-AR.These results sugges-ted that the inhibiting effects of α_1-AR and α_1A subtype on the β-AR mediated positiveinotropic response,which were shown in normal rats,were not existing,but enhancingeffect of α_1B subtype on the β-AR mediated positive inotropic response was still existingin the rats with cardiac insufficiency.

关 键 词：肾上腺素能 心功能不全 

分 类 号：R541.602[医药卫生—心血管疾病]