Bristow M R, Ginsburg R, Minobe W, Cubicciotti R S, Sageman W S, Lurie K, Billingham M E, Harrison D C, Stinson E B
N Engl J Med. 1982 Jul 22;307(4):205-11. doi: 10.1056/NEJM198207223070401.
To identify the role of the myocardial beta-adrenergic pathway in congestive heart failure, we examined beta-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 beta-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 less than 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 less than 0.05). We conclude that in failing human hearts a decrease in beta-receptor density leads to subsensitivity of the beta-adrenergic pathway and decreased beta-agonist-stimulated muscle contraction. Regulation of beta-adrenergic receptors may be an important variable in cardiac failure.
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左心室中的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。与六个功能正常的心室相比，11个衰竭的左心室β受体密度降低了50%至56%，异丙肾上腺素介导的腺苷酸环化酶最大刺激降低了45%，异丙肾上腺素刺激的最大肌肉收缩降低了54%至73%（每项比较P均小于0.05）。相比之下，两组的细胞质肌酸激酶活性、氟离子和组胺刺激的腺苷酸环化酶活性、组胺刺激的肌肉收缩以及收缩蛋白水平并无差异（P大于0.05）。我们得出结论，在衰竭的人类心脏中，β受体密度降低导致β-肾上腺素能通路反应性降低以及β激动剂刺激的肌肉收缩减弱。β-肾上腺素能受体的调节可能是心力衰竭中的一个重要变量。
