长期饮用普萘洛尔对大鼠心脏α_1肾上腺素受体亚型数量的影响

Effects of long-term propranolol treatment on number of α 1 -adrenoceptor subtypes in rat heart

采用放射配体结合实验，离体左心房收缩功能实验及逆转录聚合酶链反应等方法观察大鼠长期饮用非选择性β肾上腺素受体拮抗剂普萘洛尔（７０ｍｇ·ｋｇ－１·ｄ－１，８ｗｋ）对心脏α１肾上腺素受体（α１－ＡＲ）亚型分布及其功能的影响．结果表明大鼠饮用普萘洛尔８ｗｋ后心脏α１－ＡＲ总数量无显著变化，ＷＢ４１０１和尼古地平竞争抑制曲线两位点分析结果显示３种亚型受体所占比例发生了明显变化，α１Ａ－ＡＲ数量不变，α１Ｂ－ＡＲ数量减少，α１Ｄ－ＡＲ数量增加，α１－ＡＲ亚型ｍＲＮＡ水平的改变为α１Ａ－ＡＲ和α１Ｄ－ＡＲ显著增加，α１Ｂ－ＡＲ明显减少．但α１－ＡＲ３种亚型介导去甲肾上腺素正性变力效应的作用无显著改变．

The effects of long-term treatment with nonselective β-adrenoceptor (β-AR) antagonist propranolol (70 mg·kg -1 ·d -1 , in drinking water for 8 wk) on the expression of the adrenoceptor (α 1 -AR) subtypes and α 1 -AR mediated positive inotropic response in rats were studied by radioligand binding assay, functional determination of isolated perfused left atria and reverse transcription-polymerase chain reaction. The results indicated that after long-term propranolol treatment the density of total α 1 -AR in rat hearts was not changed, the two sites analysis of WB4101 and (+)niguldipine competitive inhibition curves showed that the ratio of three α 1 -AR subtypes were altered significantly. The number of α 1A -AR was not changed, α 1B -AR was decreased and α 1D -AR was enhanced. In mRNA levels, α 1A -AR was increased significantly, α 1B -AR was decreased and α 1D -AR was also raised. But in the isolated left atria functional experiment, the positive inotropic responses induced by activation of three α 1 -AR subtypes to norepinephrine were not changed.