Shannon Richard, Chaudhry Mohammad
Allegheny General Hospital, University School of Medicine, Pittsburgh, PA 15212, USA.
Am Heart J. 2006 Nov;152(5):842-50. doi: 10.1016/j.ahj.2006.05.017.
Compelling evidence now exists that proves adrenergic blockade is at the center of neurohormonal antagonism in heart failure (HF). Catecholamines are well known to act through both beta- and alpha-adrenergic receptors (ARs), which mediate their effects through distinct receptor pathways. Beta-AR blockers are commonly used in the treatment of HF and have distinct receptor affinity profiles. The recent COMET trial comparing 2 important beta-blocking drugs showed a distinct advantage for carvedilol in decreasing the risk of mortality from HF. The mechanism of action for carvedilol differs from metoprolol tartrate in its ability to block both alpha- and beta-ARs, leading to renewed interest in the potential role of alpha-ARs in the progression of HF. In contrast, however, the ALLHAT study discontinued use of doxazosin, an alpha1-receptor blocker because of an increase in cardiovascular events among patients using this drug. The results of these studies appear to be in contrast with respect to the role of alpha-ARs in regards to cardiovascular pathophysiology. Further study of the alpha-receptor and understanding the role of alpha-ARs in HF is necessary to understand the therapeutic effect of alpha-blockade. This article reviews our understanding of the alpha-AR in HF.
目前已有确凿证据表明，肾上腺素能阻滞是心力衰竭（HF）神经激素拮抗作用的核心。众所周知，儿茶酚胺通过β-肾上腺素能受体（AR）和α-肾上腺素能受体发挥作用，它们通过不同的受体途径介导其效应。β-AR阻滞剂常用于治疗HF，且具有不同的受体亲和力谱。最近比较两种重要β受体阻滞剂的COMET试验显示，卡维地洛在降低HF死亡率风险方面具有明显优势。卡维地洛的作用机制与酒石酸美托洛尔不同，它能够同时阻断α-AR和β-AR，这使得人们重新关注α-AR在HF进展中的潜在作用。然而，相比之下，ALLHAT研究停止使用α1受体阻滞剂多沙唑嗪，因为使用该药物的患者心血管事件增加。这些研究结果在α-AR在心血管病理生理学中的作用方面似乎相互矛盾。进一步研究α受体并了解α-AR在HF中的作用对于理解α阻滞剂的治疗效果是必要的。本文综述了我们对HF中α-AR的认识。
