Zacharia Joseph, Hillier Chris, Tanoue Akito, Tsujimoto Gozoh, Daly Craig J, McGrath John C, MacDonald Allan
Vascular Biology Group, Department of Biological & Biomedical Sciences, School of Life Sciences, Glasgow Caledonian University, Cowcaddens Road, Glasgow G4 0BA, Scotland, UK.
Br J Pharmacol. 2005 Dec;146(7):942-51. doi: 10.1038/sj.bjp.0706395.
The role of alpha(1D)-adrenoceptors in vasoconstrictor responses to noradrenaline in mouse femoral resistance arteries was investigated using wire myography in alpha(1D)-adrenoceptor knockout (alpha(1D)-KO) and wild-type (WT) mice of the same genetic background.alpha(1D)-KO mice were 2.5-fold less sensitive than WTs to exogenous noradrenaline and BMY 7378 was significantly less potent against noradrenaline in alpha(1D)-KO mice than in WTs, showing a minor contribution of alpha(1D)-adrenoceptors in response to noradrenaline. Prazosin and 5-methyl-urapidil were equally effective against noradrenaline in alpha(1D)-KO and WT mice. Chloroethylclonidine produced a significantly greater attenuation of the response to noradrenaline in alpha(1D)-KO mice than in WTs. Responses to electrical field stimulation (EFS), at 2-20 Hz for 10 s and 0.09 ms pulse width were significantly smaller overall in alpha(1D)-KOs than in WTs although no significant differences were seen at the different frequencies.BMY 7378 produced significantly greater inhibition of responses at 2 and 5 Hz than at higher frequencies in WTs. In alpha(1D)-KOs, this greater sensitivity to BMY 7378 at lower frequencies was not apparent, confirming that the effect of BMY 7378 was due to blockade of alpha(1D)-adrenoceptors. Prazosin and 5-methyl-urapidil had similar inhibitory effects on responses to EFS in alpha(1D)-KO and WT mice. Chloroethylclonidine inhibited responses to EFS to a significantly greater extent in alpha(1D)-KO mice. The present study with alpha(1D)-KO mice shows that alpha(1D)-adrenoceptors contribute to vasoconstrictor responses to exogenous and neurally released noradrenaline in femoral resistance arteries.
利用线肌动描记法，在具有相同遗传背景的α（1D）-肾上腺素能受体基因敲除（α（1D）-KO）小鼠和野生型（WT）小鼠中，研究了α（1D）-肾上腺素能受体在小鼠股部阻力动脉对去甲肾上腺素的血管收缩反应中的作用。α（1D）-KO小鼠对外源性去甲肾上腺素的敏感性比WT小鼠低2.5倍，并且在α（1D）-KO小鼠中，BMY 7378对去甲肾上腺素的效力明显低于WT小鼠，表明α（1D）-肾上腺素能受体在对去甲肾上腺素的反应中贡献较小。哌唑嗪和5-甲基乌拉地尔在α（1D）-KO小鼠和WT小鼠中对去甲肾上腺素的作用相同。氯乙可乐定在α（1D）-KO小鼠中对去甲肾上腺素反应的减弱程度明显大于WT小鼠。在2至20Hz频率下持续10秒、脉冲宽度为0.09毫秒的电场刺激（EFS）反应，尽管在不同频率下未观察到显著差异，但α（1D）-KO小鼠总体上比WT小鼠小得多。BMY 7378在WT小鼠中对2Hz和5Hz反应的抑制作用明显大于更高频率。在α（1D）-KO小鼠中，在较低频率下对BMY 7378的这种更高敏感性不明显，证实了BMY 7378的作用是由于阻断了α（1D）-肾上腺素能受体。哌唑嗪和5-甲基乌拉地尔对α（1D）-KO小鼠和WT小鼠对EFS的反应具有相似的抑制作用。氯乙可乐定在α（1D）-KO小鼠中对EFS反应的抑制作用明显更大。本研究对α（1D）-KO小鼠的研究表明，α（1D）-肾上腺素能受体在股部阻力动脉对外源性和神经释放的去甲肾上腺素的血管收缩反应中起作用。
