12月龄与3月龄大鼠心脏α1肾上腺素受体亚型的比较

Comparison of cardiac α1adrenoceptor subtypes between 12monthold and 3monthold Wistar rats1

采用［１２５Ｉ］ＢＥ２２５４放射配体结合实验和离体灌流左心房收缩功能实验，比较１２月龄与３月龄大鼠心脏α１肾上腺素受体（α１－ＡＲ）三种亚型分布及其介导的正性变力效应的差别．结果显示与３月龄大鼠相比，１２月龄大鼠：（１）心脏α１－ＡＲ最大结合容量显著减少；去甲肾上腺素（ＮＥ）通过激动α１－ＡＲ引起的左心房累积浓度－收缩效应曲线显著右移；（２）（＋）尼古地平，ＢＭＹ７３７８和ＷＢ４１０１的高亲和性位点所占百分比显著下降；（３）氯乙基可乐定预处理使ＮＥ引起的左心房最大收缩效应的下降幅度，以及舍吲哚，ＢＭＹ７３７８和ＷＢ４１０１拮抗ＮＥ介导正性变力效应的ｐＡ２值均无显著差异．提示１２月龄大鼠较３月龄大鼠心脏α１－ＡＲ总数减少，且以α１Ａ－和α１Ｄ－ＡＲ亚型更为显著；α１－ＡＲ介导的正性变力效应明显降低，α１Ｂ－ＡＲ的功能效率降低最为明显．

Differences of distribution and positive inotropic response of cardiac α1adrenoceptor (α1AR) and its subtypes between 12monthold and 3monthold Wistar rats were investigated by radioligand binding assay and isolated atria contractile response measurement. Compared with 3monthold Wistar rats, in 12monthold rats (1) the density of cardiac α1AR was reduced and the concentrationcontractile response curve for nor epinephrine(NE) was shifted to the right significantly; (2) the percentages of high affinity sites for BMY7378, WB4101 and (+)niguldipine were decreased; (3) chlorethylclonidine pretreatment shifted the concentrationresponse curve for NE to the right both in 12monthold and 3monthold rats with no difference; the pA2 values for sertindole, BMY7378 and WB4101 antagonisting NEinduced positive inotropic response were not different as well. The results suggest that in 12monthold rats, compared with 3monthold rats, the density of cardiac α1AR and the α1AR mediated contraction are decreased, especially in α1A and α1DAR subtypes. The α1AAR mediated positive inotropic response is reduced as well. The functional efficiency of α1BAR is mostly declined.