Correlation between vasoconstrictor roles and mRNA expression of α1-adrenoceptor subtypes in blood vessels of genetically engineered mice
Correlation between vasoconstrictor roles and mRNA expression of α1-adrenoceptor subtypes in blood vessels of genetically engineered mice
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DOI：
10.1038/sj.bjp.0706325
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发表时间：
2005-10-01
影响因子：
7.3
通讯作者：
Koike, K
中科院分区：
文献类型：
--
作者：
Hosoda, C;Tanoue, A;Koike, K
1我们研究了去甲肾上腺素（NAd）引起的小鼠胸主动脉和肠系膜动脉收缩中α（1）-肾上腺素受体（AR）各亚型的作用。与野生型（WT）小鼠胸主动脉中NAd的浓度-反应曲线（CRCs）相比，突变小鼠的CRCs显示出显著较低的敏感性。pD（2）值按等级顺序如下：WT小鼠（8.21）> α（1B）-肾上腺素受体敲除（α（1B）- KO）（7.77）> α（1D）-AR敲除（α（1D）-KO）（6.44）> α（1B）-和α（1D）-AR双敲除（α（1BD）-KO）（5.15）。在肠系膜动脉中，WT（6.52）和alpha（1B）-KO小鼠（7.12）或alpha（1D）-KO（6.19）和alpha（1BD）-KO（6.29）小鼠之间NAd的CRC没有显着差异。然而，α（1D）-和α（1BD）-KO小鼠对NAd的CRC最大反应显著低于WT和α（1B）-KO小鼠。2除α（1BD）-KO小鼠的胸主动脉外，竞争性拮抗剂哌唑嗪以高亲和力抑制对NAd的收缩反应。然而，哌唑嗪在缺乏α（1D）-AR基因的小鼠血管中产生浅的Schild斜率。在胸主动脉中，WT小鼠中KMD-3213和BMY 7378的pA（2）值分别为8.25和8.46，α（1B）-KO小鼠中分别为8.49和9.13。在肠系膜动脉中，WT小鼠中KMD-3213和BMY 7378的pA（2）值分别为8.34和7.47，α（1B）-KO小鼠中分别为8.11和7.82。这些药理学结果与CRC比较结果相当一致，WT和α（1B）-KO小鼠的肠系膜动脉除外，我们对这些血管中每种α（1）-AR亚型的mRNA表达进行了定量分析，以检查mRNA表达水平与每种α（1）-AR亚型优势之间的相关性。AR亚型在介导血管收缩中的作用。4每种α（1）-AR亚型在其血管收缩作用方面的等级顺序与每种亚型的mRNA表达水平相当一致，即在胸主动脉中α（1D）-AR > α（1B）-AR > α（1A）-AR，在肠系膜动脉中α（1D）-AR > α（1A）-AR > α（1B）-AR。在药理学或定量mRNA表达分析中未观察到突变小鼠中α（1）-AR亚型的显著代偿性变化。
1 We examined the contribution of each alpha(1)-adrenoceptor (AR) subtype in noradrenaline (NAd)evoked contraction in the thoracic aortas and mesenteric arteries of mice. Compared with the concentration-response curves (CRCs) for NAd in the thoracic aortas of wild-type (WT) mice, the CRCs of mutant mice showed a significantly lower sensitivity. The pD(2) value in rank order is as follows: WT mice (8.21) > alpha(1B)-adrenoceptor knockout (alpha(1B)- KO) (7.77) > alpha(1D)-AR knockout (alpha(1D)-KO) (6.44) > alpha(1B)-and alpha(1D)-AR double knockout (alpha(1BD)-KO) (5.15). In the mesenteric artery, CRCs for NAd did not differ significantly between either WT (6.52) and alpha(1B)-KO mice (7.12) or alpha(1D)-KO (6.19) and alpha(1BD)-KO (6.29) mice. However, the CRC maximum responses to NAd in alpha(1D)-and alpha(1BD)-KO mice were significantly lower than those in WT and alpha(1B)-KO mice.2 Except in the thoracic aortas of alpha(1BD)-KO mice, the competitive antagonist prazosin inhibited the contraction response to NAd with high affinity. However, prazosin produced shallow Schild slopes in the vessels of mice lacking the alpha(1D)-AR gene. In the thoracic aorta, pA(2) values in WT mice for KMD-3213 and BMY7378 were 8.25 and 8.46, respectively, and in alpha(1B)-KO mice they were 8.49 and 9.13, respectively. In the mesenteric artery, pA(2) values in WT mice for KMD-3213 and BMY7378 were 8.34 and 7.47, respectively, and in alpha(1B)-KO mice they were 8.11 and 7.82, respectively. These pharmacological findings were in fairly good agreement with findings from comparison of CRCs, with the exception of the mesenteric arteries of WT and alpha(1B)-KO mice, which showed low affinities to BMY7378.3 We performed a quantitative analysis of the mRNA expression of each alpha(1)-AR subtype in these vessels in order to examine the correlation between mRNA expression level and the predominance of each alpha(1)-AR subtype in mediating vascular contraction.4 The rank order of each alpha(1)-AR subtype in terms of its vasoconstrictor role was in fairly good agreement with the level of expression of mRNA of each subtype, that is, alpha(1D)-AR >alpha(1B)-AR >alpha(1A)-AR in the thoracic aorta and alpha(1D)-AR >alpha(1A)-AR >alpha(1B)-AR in the mesenteric artery. No dramatic compensatory change of alpha(1)-AR subtype in mutant mice was observed in pharmacological or quantitative mRNA expression analysis.