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慢性心功不全大鼠心脏α1受体对β受体正性变力效应调节作用的改变
Altered effects of α1-adrenoceptor on β-adrenoceptor induced positive inotropic response in the rat with cardiac insufficiency
【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。
【Abstract】 The distribution of α1-adrenoceptor(α1-AR)subtypes and the effects ofactivation of α1-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 α1-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 α1A-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 α1-AR, and 1 nmol/L WB410 l which inactivated only α1A-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 α1B-AR.These results sugges-ted that the inhibiting effects of α1-AR and α1A subtype on the β-AR mediated positiveinotropic response,which were shown in normal rats,were not existing,but enhancingeffect of α1B subtype on the β-AR mediated positive inotropic response was still existingin the rats with cardiac insufficiency.
【Key words】 Receptors,adrenergic,Alpha; Receptors,adrenergic,Beta; Myocardial contrac-tion;
- 【文献出处】 中国病理生理杂志 ,CHINESE JOURNAL OF PATHOPHYSIOLOGY , 编辑部邮箱 ,1995年06期
- 【分类号】R363.21
- 【被引频次】7
- 【下载频次】61