Center for Translational Medicine and Department of Pharmacology, Lewis Katz School of Medicine, Temple University, Philadelphia, USA.
Center for Translational Medicine and Department of Pharmacology, Lewis Katz School of Medicine, Temple University, Philadelphia, USA.
Cell Signal. 2018 Jan;41:33-40. doi: 10.1016/j.cellsig.2017.01.014. Epub 2017 Jan 7.
Nitric oxide (NO), initially identified as endothelium-derived relaxing factor (EDRF), is a gaso-transmitter with important regulatory roles in the cardiovascular, nervous and immune systems. In the former, this diatomic molecule and free radical gas controls vascular tone and cardiac mechanics, among others. In the cardiovascular system, it is now understood that β-adrenergic receptor (βAR) activation is a key modulator of NO generation. Therefore, it is not surprising that the up-regulation of G protein-coupled receptor kinases (GRKs), in particular GRK2, that restrains βAR activity contributes to impaired cardiovascular functions via alteration of NO bioavailability. This review, will explore the specific interrelation between βARs, GRK2 and NO in the cardiovascular system and their inter-relationship for the pathogenesis of the onset of disease. Last, we will update the readers on the current status of GRK2 inhibitors as a potential therapeutic strategy for heart failure with an emphasis on their ability of rescuing NO bioavailability.
一氧化氮（NO）最初被鉴定为内皮衍生的松弛因子（EDRF），是一种在心血管、神经和免疫系统中具有重要调节作用的气体递质。在心血管系统中，β肾上腺素能受体（βAR）的激活是一氧化氮产生的关键调节剂。因此，G 蛋白偶联受体激酶（GRK）的上调，特别是抑制βAR 活性的 GRK2 的上调，通过改变一氧化氮的生物利用度，导致心血管功能受损，这并不奇怪。这篇综述将探讨βAR、GRK2 和 NO 在心血管系统中的特定相互关系及其在疾病发病机制中的相互关系。最后，我们将更新读者关于 GRK2 抑制剂作为心力衰竭潜在治疗策略的最新情况，重点介绍它们恢复一氧化氮生物利用度的能力。
