12月龄自发性高血压大鼠心脏α_1肾上腺素受体亚型的改变

Alterations of α 1-adrenoceptor subtypes in heart of 12 month-old spontaneously hypertensive rats

目的和方法：采用１２５Ｉ－ＢＥ２２５４放射配基结合实验和离体灌流左心房收缩功能实验，观察１２月龄自发性高血压大鼠（ＳＨＲ）心脏α１肾上腺素受体（α１－ＡＲ）３种亚型的分布及其介导的正性变力效应的改变。结果：ＳＨＲ与年龄匹配的Ｗｉｓｔａｒ大鼠相比，（１）心脏α１－ＡＲ最大结合容量显著增加；去甲肾上腺素（ＮＥ）通过激动α１－ＡＲ引起的累积浓度－收缩效应曲线显著左移；（２）ＢＭＹ７３７８和ＷＢ４１０１的高亲和性位点所占百分比显著增大，而（＋）ｎｉｇｕｌｄｉｐｉｎｅ不变；（３）经ＣＥＣ预处理引起ＮＥ累积浓度－收缩效应曲线右移的程度显著增加，ＢＭＹ７３７８和ＷＢ４１０１拮抗ＮＥ介导正性变力效应的ｐＡ２值均显著增大。结论：ＳＨＲ较同龄Ｗｉｓｔａｒ大鼠心脏α１－ＡＲ总数增多，对ＮＥ的敏感性显著增高，α１Ｄ－ＡＲ不仅数量增多，而且在介导收缩效应中的作用亦显著增大。

AIM and METHOD:Alterations of cardiac α 1-adrenoceptor (α 1-AR) and its subtypes in 12 month-old spontaneously hypertensive rats (SHR) were investigated by radioligand binding assay and contractile response measurement. RESULTS:Compared with the age-matched Wistar rats,in SHR (1) The density of cardiac α 1-AR was increased and the concentration-contractile response curve for norepinephrine (NE) was shifted to the left significantly;(2)The percentages of high affinity sites for BMY7378 and WB4101 were increased and significantly for (+) niguldipine was not changed; (3)Chloroethylconidine pretreatment shifeted the concentration-response curve for NE to the right both in SHR and Wister rats,but the shift was much greater in the former;the pA 2 values for BMY7378 and WB4101 on antagonizing NE-induced positive inotropic response were increased significantly. CONCLUSION:The total number of cardiac α 1-AR and the α 1-AR mediated contraction are increased in SRH.The Change is α 1D selective.