Subtype specific regulation of human vascular α1-adrenergic receptors by vessel bed and age
Subtype specific regulation of human vascular α1-adrenergic receptors by vessel bed and age
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DOI：
10.1161/01.cir.100.23.2336
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发表时间：
1999-12-07
期刊：
影响因子：
37.8
通讯作者：
Schwinn, DA
中科院分区：
文献类型：
--
作者：
Rudner, XL;Berkowitz, DE;Schwinn, DA
背景-α(1)-肾上腺素能受体(α(1)-ARs)调节血压、局部血管阻力和静脉容量：介导这些作用的确切亚型(α(1a)、α(1b)、α(1d))尚不清楚，且随所研究物种的不同而不同。为了了解心血管对急性应激和慢性儿茶酚胺暴露的反应机制，我们检验了两个假设：(1)人类α(1)AR亚型的表达随血管床的不同而不同，(2)年龄影响人类血管α(1)AR亚型的表达。方法和结果-384例患者的500条血管在mRNA和蛋白水平上检测了α(1)AR亚型的分布(核糖核酸酶保护试验、配体结合试验、收缩试验)。总的血管α(1)AR密度为16+/-2.3fmol/mg总蛋白。α(1a)AR主要存在于动脉中的m RNA(P<；0.001)和蛋白质(P<；0.05)水平；所有3种亚型都存在于静脉中。此外，(α(1)AR mRNA亚型的表达随着血管床的不同而不同(α(1a)在内脏动脉高于中央动脉，P<；0.05)；竞争分析(选定的血管)和功能分析表明α(1a)和α(1b)介导的乳动脉收缩。结论人血管α(1)AR亚型分布与动物模型不同，随血管床的不同而不同，与乳腺动脉收缩相关，并受年龄的调节。这些发现为许多临床环境中的治疗干预提供了潜在的新靶点。
Background-alpha(1)-adrenergic receptors (alpha(1)ARs) regulate blood pressure, regional vascular resistance, and venous capacitance: the exact subtype (alpha(1a), alpha(1b), alpha(1d)) mediating these effects is unknown and varies with species studied. In order to understand mechanisms underlying cardiovascular responses to acute stress and chronic catecholamine exposure las seen with aging), we tested two hypotheses: (1) human alpha(1)AR subtype expression differs with vascular bed, and (2) age influences human vascular alpha(1)AR subtype expression.Methods and Results-Five hundred vessels from 384 patients were examined for alpha(1)AR subtype distribution at mRNA and protein levels (RNase protection assays, ligand binding, contraction assays). Overall vessel alpha(1)AR density is 16 +/- 2.3 fmol/mg total protein. alpha(1a)AR predominates in arteries at mRNA (P < 0.001) and protein (P < 0.05) levels; all 3 subtypes are present in veins. Furthermore, (alpha(1)AR mRNA subtype expression varies with vessel bed (alpha(1a) higher in splanchnic versus central arteries, P < 0.05); competition analysis (selected vessels) and functional assays demonstrate alpha(1a) and alpha(1b)-mediated mammary artery contraction. Overall alpha(1)AR expression doubles with age (alpha(1a) expression (P less than or equal to 0.001).Conclusions-Human vascular alpha(1)AR subtype distribution differs from animal models, varies with vessel bed, correlates with contraction in mammary artery, and is modulated by aging. These findings provide potential novel targets for therapeutic intervention in many clinical settings.