BETA-1-ADRENERGIC-RECEPTOR AND BETA-2-ADRENERGIC-RECEPTOR SUBPOPULATIONS IN NONFAILING AND FAILING HUMAN VENTRICULAR MYOCARDIUM - COUPLING OF BOTH RECEPTOR SUBTYPES TO MUSCLE-CONTRACTION AND SELECTIVE BETA-1-RECEPTOR DOWN-REGULATION IN HEART-FAILURE-
BETA-1-ADRENERGIC-RECEPTOR AND BETA-2-ADRENERGIC-RECEPTOR SUBPOPULATIONS IN NONFAILING AND FAILING HUMAN VENTRICULAR MYOCARDIUM - COUPLING OF BOTH RECEPTOR SUBTYPES TO MUSCLE-CONTRACTION AND SELECTIVE BETA-1-RECEPTOR DOWN-REGULATION IN HEART-FAILURE-
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DOI：
10.1161/01.res.59.3.297
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发表时间：
1986-09-01
影响因子：
20.1
通讯作者：
STINSON, EB
中科院分区：
文献类型：
--
作者：
BRISTOW, MR;GINSBURG, R;STINSON, EB
我们使用放射性配基结合技术和在孤立的心脏问题中测量β-激动剂介导的正性变力反应来检查无衰竭和衰竭的人左室和右室心肌中的β-肾上腺素能受体亚群。在来自48个人心脏的组织中，通过放射性配基结合在不衰竭的心室中鉴定出的受体亚型是β1(77%)和β2(23%)，没有证据表明存在“非典型的”β-肾上腺素能受体。在左心室衰竭时，β1：β2的比率明显不同，即60：38。在衰竭的心室中，β1比例的下降和β2比例的增加是由于β1亚群的“选择性”下调了62%，而β2受体的变化很小或没有变化。在来自未衰竭和衰竭右心室的分离小梁的肌浴实验中，β1和β2肾上腺素能受体均与正性肌力反应相偶联。在非衰竭心肌中，β1反应占主导地位，选择性β1激动剂地诺帕明产生的反应占异丙肾上腺素总收缩反应的66%。在心力衰竭时，β1成分显著减少，而β2成分没有显著减少。此外，在心力衰竭中，β2成分显著增加，因为对选择性β2激动剂zinterol的收缩反应从异丙肾上腺素产生的总反应的少数(39%)增加到多数(60%)。我们得出结论，衰竭的人类心肌含有相对较高比例的β2受体，这是由于β1受体的选择性下调。因此，在衰竭的人心脏中，β2受体亚群是对非选择性β激动剂刺激作出反应的变力支持的相对重要的中介，并且可用于选择性β2激动剂的变力刺激。
We used radioligand binding techniques and measurement of .beta.-agonist-mediated positive inotropic responses in isolated cardiac issue to examine .beta.-adrenergic-receptor subpopulations in nonfailing and failing human left and right ventricular myocardium. In tissue derived from 48 human hearts the receptor subtypes identified in nonfailing ventricle by radioligand binding were .beta.1 (77%) and .beta.2 (23%), with no evidence of an "atypical" .beta.-adrenergic receptor. In failing left ventricle the .beta.1:.beta.2 ratio was markedly different, i.e., 60:38. This decrease in the .beta.1 proportion and increase in the .beta.2 proportion in the failing ventricles were due to a 62%, "selective" down-regulation of the .beta.1 subpopulation, with little or no change in .beta.2 receptors. In muscle bath experiments in isolated trabeculae derived from nonfailing and failing right ventricles, both .beta.1- and .beta.2-adrenergic receptors were coupled to a positive inotropic response. In nonfailing myocardium, .beta.1 responses predominated, as the selective .beta.1 agonist denopamine produced a response that was 66% of the total contractile response of isoproterenol. In heart failure the .beta.1 component was markedly decreased, while the .beta.2 component was not significantly diminished. Moreover, in heart failure the .beta.2 component increased in prominence, as the contractile response to the selective .beta.2 agonist zinterol increased from a minority (39%) to a majority (60%) of the total response generated by isoproterenol. We conclude that failing human ventricular myocardium contains a relatively high proportion of .beta.2 receptors, due to selective down-regulation of .beta.1 receptors. As a result, in the failing human heart the .beta.2-receptor subpopulation is a relatively important mediator of inotropic support in response to nonselective .beta.-agonist stimulation and is available for inotropic stimulation by selective .beta.2 agonists.