Colucci W S
Myocardial Biology Unit, Boston University School of Medicine, Massachusetts, USA.
Clin Cardiol. 1998 Dec;21(12 Suppl 1):I20-4. doi: 10.1002/clc.4960211305.
Increased sympathetic nervous system (SNS) activity in patients with heart failure may help to support cardiovascular function. However, increased SNS activity, particularly if prolonged, may exert deleterious effects on cardiovascular structure and function by stimulating pathologic myocardial remodeling. In vitro, norepinephrine mimics many features of myocardial remodeling, including hypertrophy of individual myocytes and reinduction of fetal genes. Furthermore, stimulation of the beta-adrenergic pathway has been shown to stimulate apoptosis of cardiac myocytes in vitro, in rats infused with isoproterenol, and in mice that overexpress the stimulatory G-protein, Gs. Thus, increased SNS activity, acting via beta-adrenergic receptors, may play an important role in the progression of myocardial failure by acting directly on myocytes and other cell types in the heart to regulate fundamental biologic properties such as growth, apoptosis, and the composition of the extracellular matrix. This thesis provides a mechanism by which beta-adrenergic antagonists may inhibit or reverse pathologic remodeling, improve myocardial structure and function, and prolong patient survival.
心力衰竭患者交感神经系统（SNS）活性增加可能有助于维持心血管功能。然而，SNS活性增加，特别是如果持续时间较长，可能通过刺激病理性心肌重塑对心血管结构和功能产生有害影响。在体外，去甲肾上腺素模拟心肌重塑的许多特征，包括单个心肌细胞肥大和胎儿基因的重新诱导。此外，β-肾上腺素能途径的刺激已被证明在体外、在注射异丙肾上腺素的大鼠中以及在过表达刺激性G蛋白Gs的小鼠中可刺激心肌细胞凋亡。因此，通过β-肾上腺素能受体起作用的SNS活性增加，可能通过直接作用于心肌细胞和心脏中的其他细胞类型来调节生长、凋亡和细胞外基质组成等基本生物学特性，从而在心肌衰竭的进展中起重要作用。这一论点为β-肾上腺素能拮抗剂抑制或逆转病理性重塑、改善心肌结构和功能以及延长患者生存期提供了一种机制。
