Feuerstein G, Yue T L, Ma X, Ruffolo R R
Cardiovascular Pharmacology, SmithKline Beecham Pharmaceuticals, Philadelphia, PA, USA.
Prog Cardiovasc Dis. 1998 Jul-Aug;41(1 Suppl 1):17-24. doi: 10.1016/s0033-0620(98)80027-3.
Carvedilol is a novel cardiovascular drug of proven efficacy in the treatment of hypertension, angina, and heart failure. Several mechanisms may account for the beneficial effects of carvedilol in patients with heart failure. As with other beta-blockers, blockade of cardiac beta-adrenergic receptors (both beta1 and beta2), and hence reduction of cardiac work load and oxygen consumption, plays an important role in the actions of this agent. Additional benefit is provided by vasodilation (alphal-adrenergic blockage) at peripheral resistance vessels, which decreases preload and after-load, thereby further reducing cardiac work and wall tensions. In addition, potential advantages of carvedilol resulting from alpha1-adrenergic blockade are likely because alpha1-adrenergic receptors mediate cardiac remodeling by inducing hypertrophy. Finally, carvedilol is a potent antioxidant and is unique among beta-blockers in this respect. In recent years, evidence has accumulated in support of the role played by reactive oxygen radicals in chronic pathological states of the myocardium. In this article, the role of oxygen radicals in heart failure is discussed with special reference to apoptosis, a phenomenon believed to be involved in progressive cardiac myocyte loss in ischemic or myopathic heart diseases. The potential role of the antioxidant actions of carvedilol, especially in prevention of apoptotic cell death, is highlighted as a novel mechanism of action in heart failure.
卡维地洛是一种新型心血管药物，在治疗高血压、心绞痛和心力衰竭方面已证实具有疗效。卡维地洛对心力衰竭患者产生有益作用可能有多种机制。与其他β受体阻滞剂一样，阻断心脏β肾上腺素能受体（β1和β2），从而降低心脏工作负荷和耗氧量，在该药物的作用中起着重要作用。外周阻力血管的血管舒张（α1肾上腺素能阻滞）可带来额外益处，这会降低前负荷和后负荷，从而进一步减少心脏工作和室壁张力。此外，卡维地洛因α1肾上腺素能阻滞而具有的潜在优势可能是因为α1肾上腺素能受体通过诱导肥大来介导心脏重塑。最后，卡维地洛是一种强效抗氧化剂，在这方面在β受体阻滞剂中独具特色。近年来，越来越多的证据支持活性氧自由基在心肌慢性病理状态中所起的作用。在本文中，将特别参考细胞凋亡来讨论氧自由基在心力衰竭中的作用，细胞凋亡被认为与缺血性或心肌病性心脏病中进行性心肌细胞丧失有关。卡维地洛抗氧化作用的潜在作用，尤其是在预防凋亡性细胞死亡方面，被强调为心力衰竭中的一种新作用机制。
