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

本研究的第一个目的是阐明α 1和α 2肾上腺素能受体（AR）在充血性心力衰竭（CHF）大鼠外周小动脉中的作用。结扎WKY大鼠左冠状动脉前壁诱发CHF。假手术大鼠作为对照。术后4周，从提睾肌处切取小动脉（φ 100 μ m），两端插入玻璃微吸管，组织浴中Krebs液灌注。我们评估了CHF大鼠小动脉对α 1-激动剂（苯丙氨酸：PE）和α 2-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组对PE的浓度-反应曲线（CRC）右移（EC_<50>（CHF）：0.97 μ M，P &lt; 0.01）。：0.30uM）。与对照组相比，CHF患者PE的最大收缩增加（vs CHF; 142%）。CHF组CRC对UK的表达较对照组左移（EC_（10）<50>; CHF组：0.05 μ M，P &lt; 0.05）。：0.26uM）。与对照组相比，CHF患者对UK的最大收缩减少（vs.占76%。结果表明：CHF时，α 1-AR的最大微动脉收缩力增强，亲和力降低，而α 2-AR的最大微动脉收缩力减弱，亲和力增强。α 1-和α 2-AR可能在CHF外周小动脉反应的调节中发挥不同的作用。本研究的第二个目的是探讨CHF时α 2小动脉收缩功能改变的机制。两组间差异无统计学意义。提示CHF时α 2-AR与VDCC之间的相互作用机制改变了α 2-AR的收缩功能。

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.