Contractile and relaxant effects of b2- and b1-adrenoceptors in human heart: blockade by a third generation b-blocker

在影响心脏的疾病状态下，每次心跳的力度和持续时间可以改变。它们也可以被体内自然产生的化学物质修饰。影响心脏功能的两种最重要的天然化学物质是（-）去甲肾上腺素和（-）肾上腺素。这些化学物质和其他已合成和优化的化学物质也可用于治疗。它们的工作原理是激活细胞表面的一种叫做b-肾上腺素受体的蛋白质。当b-肾上腺素受体被激活时，会导致每次心跳力度的增加和每次心跳持续时间的缩短。在心脏跳动过长的情况下，这可能是一个优势。在这项研究中，我们建议绘制通过b-肾上腺素受体影响每次心跳的生化途径。由于使用阻断b-肾上腺素受体的化合物，心力衰竭的治疗管理已经发生了革命性的变化。其中一种药物，卡维地洛目前在这个国家使用。它的工作方式可能还没有被完全理解。在初步的实验中，我们已经确定了卡维地洛直接作用于人类心脏的一种新机制，在这种机制中，卡维地洛可能起作用，并有助于它在治疗心力衰竭方面的有益作用。我们的研究将集中在这个发现上。

The force and the duration of each heart beat can be modified in disease states affecting the heart. They can also be modified by chemicals which occur naturally in the body. Two of the most important naturally occurring chemicals which affect the function of the heart are (-)-noradrenaline and (-)-adrenaline. These chemicals and others which have been synthesized and optimized can also be used therapeutically. They work by activating proteins which occur on the cell surface, called b-adrenoceptors. When activated, b-adrenoceptors cause an increase in the force of each heart beat and a reduction in the duration of each heart beat. This may be an advantage in conditions where the heart beat is too long. In this study we propose to map the biochemical pathways through which b-adrenoceptors affect each heart beat. The therapeutic management of heart failure has been revolutionized by the use of compounds which block b-adrenoceptors. One such drug, carvedilol is currently used in this country. The way in which it works may not be fully understood. In preliminary experiments we have identified a novel mechanism for carvedilol directly in human heart in which it may work and contribute to it's beneficial effects in the management of heart failure. Our studies will focus on this finding.