Movsesian M A
Salt Lake City VA Medical Center, University of Utah School of Medicine, USA.
J Am Coll Cardiol. 1999 Aug;34(2):318-24. doi: 10.1016/s0735-1097(99)00220-x.
Clinical trials of beta-adrenergic receptor agonists and cyclic nucleotide phosphodiesterase inhibitors in heart failure have demonstrated a reduction in survival in treated patients despite initial inotropic responses. These findings have led many to infer that activation of the mechanisms through which contractility is increased has deleterious effects on failing myocardium. It should be remembered, however, that these agents act proximately by raising intracellular cyclic adenosine monophosphate (cAMP) content and stimulating protein phosphorylation by cAMP-dependent protein kinase, and that the proteins whose phosphorylation contributes to the inotropic responses may be different from the proteins whose phosphorylation contributes to the reduction in survival. Evidence in support of the latter interpretation is presented, and potential therapeutic approaches through which the phosphorylation of different proteins might be selectively affected are considered.
β-肾上腺素能受体激动剂和环核苷酸磷酸二酯酶抑制剂用于心力衰竭的临床试验表明，尽管初始有正性肌力反应，但治疗患者的生存率却降低了。这些发现使许多人推断，通过增加心肌收缩力的机制激活对衰竭心肌有有害影响。然而，应该记住，这些药物的直接作用是通过提高细胞内环磷酸腺苷（cAMP）含量并刺激cAMP依赖性蛋白激酶进行蛋白磷酸化，并且其磷酸化有助于正性肌力反应的蛋白质可能与那些磷酸化导致生存率降低的蛋白质不同。本文提供了支持后一种解释的证据，并考虑了可能选择性影响不同蛋白质磷酸化的潜在治疗方法。
