Le Tran Y, Forster C
Department of Pharmacology, University of Toronto, Ontario, Canada.
Eur J Pharmacol. 1997 Oct 8;336(2-3):177-85. doi: 10.1016/s0014-2999(97)01243-0.
This study examined the interaction of chloroethylclonidine with alpha-adrenoceptor agonists in canine endothelium-denuded dorsal pedal artery and saphenous vein before (non-paced) and at end-stage heart failure which was induced by rapid ventricular pacing (250 bpm for no more than four weeks). The interaction was heterogeneous in both non-paced and heart failure blood vessels. In the dorsal pedal artery, only chloroethylclonidine (10(-4) M) reduced the maximum response to noradrenaline. At 10(-6) and 10(-5) M, chloroethylclonidine potentiated the response to noradrenaline. In the saphenous vein, chloroethylclonidine was not surmountable against noradrenaline before heart failure, but produced competitive antagonism of noradrenaline in the heart failure group (pA2 = 5.7). In the dorsal pedal artery, chloroethylclonidine potentiated the response to low concentrations of methoxamine, but inhibited the response of higher concentrations. In the saphenous vein, chloroethylclonidine (10(-6) and 10(-5) M) potentiated the response to methoxamine from non-paced dogs but did not significantly effect the response at heart failure. In the dorsal pedal artery, chloroethylclonidine (10(-4) M) potentiated low concentrations and inhibited higher concentrations of phenylephrine from non-paced animals but had no significant effect at heart failure. In contrast, in the saphenous vein, chloroethylclonidine (at all concentrations tested) inhibited the response to phenylephrine in non-paced dogs, whereas the inhibitory effect was not as marked in heart failure. In conclusion, these results indicate that differences in alpha1-adrenoceptor populations and distribution are blood vessel dependent and dependent on the pathological state.
本研究检测了氯乙可乐定与α-肾上腺素能受体激动剂在犬内皮剥脱的足背动脉和大隐静脉中的相互作用，实验分别在快速心室起搏（250次/分钟，不超过四周）诱导的心衰前期（非起搏状态）和终末期进行。在非起搏和心衰血管中，这种相互作用都是异质性的。在足背动脉中，只有氯乙可乐定（10⁻⁴M）降低了对去甲肾上腺素的最大反应。在10⁻⁶和10⁻⁵M时,氯乙可乐定增强了对去甲肾上腺素的反应。在大隐静脉中，氯乙可乐定在心衰前对去甲肾上腺素的拮抗作用不可克服，但在心力衰竭组中对去甲肾上腺素产生竞争性拮抗作用（pA2 = 5.7）。在足背动脉中，氯乙可乐定增强了对低浓度甲氧明的反应，但抑制了高浓度甲氧明的反应。在大隐静脉中，氯乙可乐定（10⁻⁶和10⁻⁵M）增强了非起搏犬对甲氧明的反应，但对心衰时的反应没有显著影响。在足背动脉中，氯乙可乐定（10⁻⁴M）增强了非起搏动物低浓度苯肾上腺素的反应并抑制了高浓度苯肾上腺素的反应，但在心衰时没有显著影响。相反，在大隐静脉中，氯乙可乐定（在所有测试浓度下）抑制了非起搏犬对苯肾上腺素的反应，而在心力衰竭时这种抑制作用不明显。总之，这些结果表明α1-肾上腺素能受体的数量和分布差异取决于血管类型和病理状态。
