Nomura S, Sunagane N, Lee T J, Uruno T, Kubota K
Drug Safety Research 3, Tsukuba Research Laboratories, Tsukuba, Japan.
Res Commun Mol Pathol Pharmacol. 1995 Dec;90(3):307-20.
The effects of alpha2-adrenoceptor agonists, clonidine, tizanidine and UK-14304 on alpha1-adrenoceptor-mediated contractile responses were studied in isolated tail arteries and thoracic aorta of the rat. When applied during sustained contractile responses to almost maximum concentration (10 microM) of phenylephrine, clonidine (0.3 microM to 100 microM) produced concentration-dependent relaxations in both tissues. The maximum relaxation was smaller in tail arteries than in thoracic aorta. Clonidine up to 100 microM failed to relax both tissues precontracted with KCl (60 microM) or U-46619 (1 microM), a thromboxane mimetic. The clonidine-induced relaxation in tail arteries, was reversed by alpha2-adrenoceptor antagonists, yohimbine and idazoxane. Effects of the alpha2-adrenoceptor antagonists were concentration-dependent (0.1 microM to 1 microM), but not in a competitive manner. On the other hand, the relaxation in thoracic aorta was not significantly antagonized by these alpha2-adrenoceptor antagonists. Tizanidine and UK-14304 also relaxed both tail arteries and thoracic aorta precontracted with phenylephrine. The characteristics of the relaxation and their antagonism by yohimbine in both arteries were similar to those induce by clonidine. In tail arteries, NG-nitro-L-arginine, a nitric oxide synthase inhibitor, at a concentration that completely inhibited acetylcholine-induced relaxations did not significantly affect the relaxation induced by clonidine. In contrast, the relaxation of thoracic aorta in response to clonidine was partly reduced in the presence of NG-nitro-L-arginine. These results indicate that the alpha2-adrenoceptor agonists selectively inhibit the contractions induced by phenylephrine in both tissues. Regional differences in the modes of the inhibition by the alpha2-adrenoceptor agonists exist.
研究了α2-肾上腺素能受体激动剂可乐定、替扎尼定和UK-14304对大鼠离体尾动脉和胸主动脉中α1-肾上腺素能受体介导的收缩反应的影响。当在对几乎最大浓度（10μM）去氧肾上腺素的持续收缩反应期间应用时，可乐定（0.3μM至100μM）在两种组织中均产生浓度依赖性舒张。尾动脉中的最大舒张幅度小于胸主动脉。高达100μM的可乐定未能使预先用氯化钾（60μM）或血栓素类似物U-46619（1μM）预收缩的两种组织舒张。可乐定诱导的尾动脉舒张可被α2-肾上腺素能受体拮抗剂育亨宾和咪唑克生逆转。α2-肾上腺素能受体拮抗剂的作用呈浓度依赖性（0.1μM至1μM），但并非竞争性作用。另一方面，这些α2-肾上腺素能受体拮抗剂并未显著拮抗胸主动脉的舒张。替扎尼定和UK-14304也使预先用去氧肾上腺素预收缩的尾动脉和胸主动脉舒张。育亨宾对两条动脉舒张及其拮抗作用的特征与可乐定诱导的相似。在尾动脉中，一氧化氮合酶抑制剂NG-硝基-L-精氨酸在完全抑制乙酰胆碱诱导的舒张的浓度下，并未显著影响可乐定诱导的舒张。相反，在存在NG-硝基-L-精氨酸的情况下，可乐定引起的胸主动脉舒张部分减弱。这些结果表明，α2-肾上腺素能受体激动剂在两种组织中均选择性抑制去氧肾上腺素诱导的收缩。α2-肾上腺素能受体激动剂的抑制方式存在区域差异。
