Modification in the peripheral arteriole alpha-adrenoceptor subtype by congestive heart failure.

本研究的第一个目的是阐明α1和α2肾上腺素受体(AR)在充血性心力衰竭(CHF)大鼠外周小动脉中的作用。采用左冠状动脉前支结扎法建立WKY大鼠心力衰竭模型。假手术组大鼠作为对照。术后4周，从提睾肌中分离出小动脉(Phi100um)，两端植入玻璃微针，在组织浴中用Krebs液灌流。我们评估了CHF大鼠动脉对α1激动剂(苯肾上腺素：PE)和α2激动剂(UK-14,304：UK)的反应，并与对照组进行了比较。与对照组相比，CHF患者对PE的量效曲线(CRC)右移(EC；50；CHF：0.97微米，续)。：0.30uM)。与对照组相比，CHF组对PE的最大收缩增加(比对照组增加142%)。与对照组相比，CHF患者的CRC向UK左移(EC_&lt；50；CHF：0.05uM，续)。：0.26微米)。与对照组相比，充血性心力衰竭患者对UK的最大收缩功能降低(vs.；76%)。结果表明，CHF时α1-AR的最大小动脉收缩增加，α1-AR的亲和力降低，而α2-AR的最大小动脉收缩减少，α2-AR的亲和力增加。α1-AR和α2-AR在CHF外周小动脉反应的调节中可能起不同的作用。本研究的第二个目的是探讨CHF时α2微动脉收缩的变化机制。两组间差异无统计学意义。提示CHF时，α2-AR和VDCC之间的相互作用机制改变了α2-微动脉收缩。

The first aim of this study is to clarify the role of alpha1-and alpha2-adrenoceptor (AR) in the peripheral arteriole of rats with congestive heart failure (CHF). CHF was induced in WKY rats by left anterior coronary artery ligation. Sham-operated rats served as a control. An arteriole (phi100um) was dissected out from the cremaster and was inserted glass micropippettes from both ends, and was perfused by Krebs solution in tissue bath 4 weeks after operation. We evaluated responses in the arterioles from CHF rats to alpha1-agonists (phenylphrine : PE) and alpha2-agonists (UK-14,304 : UK), compared with those of a control. Concentration-response curves (CRC) to PE in CHF was shifted to the right compared with a control (EC_<50> ; CHF : 0.97uM,cont. : 0.30uM). Maximal contraction to PE was increased in CHF compared with a control (vs cont ; 142%). CRC to UK in CHF was shifted to the left compared with a control (EC_<50> ; CHF : 0.05uM,cont. : 0.26uM). Maximal contraction to UK was decreased in CHF compared with a control (vs cont. ; 76%). Our data shows that in CHF,maximal arteriole constriction of alpha1-AR increased but the affinity of alpha1-AR decreased, in contrast, maximal arteriole constriction of alpha2-AR decreased but the affinity of alpha2-AR increased. alpha1-and alpha2-AR may play the different roles in the regulation of the peripheral arteriolar responses in CHF.The second goal of this study is to test the mechanism of the alteration of alpha2 arteriole constriction in CHF.The CRCs of Bay K-8644, L-type voltage-dependent Ca^<2+> channel (VDCC) agonist, were tested CHF and control rats. There was no significant difference between two groups. This date suggest that alpha2 arteriole constriction was altered in CHF through mechanism that involve between alpha2-AR and VDCC.