DECREASED CATECHOLAMINE SENSITIVITY AND BETA-ADRENERGIC-RECEPTOR DENSITY IN FAILING HUMAN HEARTS
DECREASED CATECHOLAMINE SENSITIVITY AND BETA-ADRENERGIC-RECEPTOR DENSITY IN FAILING HUMAN HEARTS
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DOI：
10.1056/nejm198207223070401
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发表时间：
1982-01-01
影响因子：
158.5
通讯作者：
STINSON, EB
中科院分区：
文献类型：
--
作者：
BRISTOW, MR;GINSBURG, R;STINSON, EB
为了确定心肌β肾上腺素能通路在充血性心力衰竭中的作用，我们检测了心脏移植受者或潜在供体的衰竭心脏和功能正常心脏的左心室中β肾上腺素能受体密度、腺苷酸环化酶和肌酸激酶活性、体外肌肉收缩以及心肌收缩蛋白水平。与6个功能正常的心室相比，11个衰竭的左心室β受体密度降低50%~ 56%，最大异丙肾上腺素介导的腺苷酸环化酶刺激降低45%，最大异丙肾上腺素刺激的肌肉收缩降低54%~ 73%（每次比较P<0.05）。而氟离子和组胺刺激的肌浆肌酸激酶活性、腺苷酸环化酶活性、组胺刺激的肌收缩及收缩蛋白水平在两组间无显著性差异（P>0.05）。我们的结论是，在衰竭的人类心脏中，β受体密度的降低导致β肾上腺素能通路的亚敏感性和β激动剂刺激的肌肉收缩的降低。β-肾上腺素能受体的调节可能是心力衰竭的一个重要变量。（《新英格兰医学杂志》，1982年; 307：205- 211）
To identify the role of the myocardial β-adrenergic pathway in congestive heart failure, we examined β-adrenergic-receptor density, adenylate cyclase and creatine kinase activities, muscle contraction in vitro, and myocardial contractile protein levels in the left ventricles of failing and normally functioning hearts from cardiac-transplant recipients or prospective donors. Eleven failing left ventricles had a 50 to 56 per cent reduction in β-receptor density, a 45 per cent reduction in maximal isoproterenol-mediated adenylate cyclase stimulation, and a 54 to 73 per cent reduction in maximal isoproterenol-stimulated muscle contraction, as compared with six normally functioning ventricles (P<0.05 for each comparison). In contrast, cytoplasmic creatine kinase activity, adenylate cyclase activities stimulated by fluoride ion and by histamine, histamine-stimulated muscle contraction, and levels of contractile protein were not different in the two groups (P>0.05). We conclude that in failing human hearts a decrease in β-receptor density leads to subsensitivity of the β-adrenergic pathway and decreased β-agonist-stimulated muscle contraction. Regulation of β-adrenergic receptors may be an important variable in cardiac failure. (N Engl J Med. 1982; 307:205–11.)