12月龄与3月龄大鼠心脏α1肾上腺素受体亚型的比较

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α_1A和α_1D-AR亚型更为显著; α₁-AR介导的正性变力效应明显降低, α_1B-AR的功能效率降低最为明显.

Comparison of cardiac α1-adrenoceptor subtypes between 12-month-old and 3- month-old Wistar rats

Differences of distribution and positive inotropic response of cardiac α₁- adrenoceptor (α₁-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 α₁- 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 pA₂ 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 α₁- AR and the α₁-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.