Pole of Pharmacology and Therapeutics, Institut de Recherche Experimentale et Clinique, Brussels, Belgium.
Cardiovasc Res. 2012 May 1;94(2):304-15. doi: 10.1093/cvr/cvr360. Epub 2012 Jan 6.
The three isoforms of nitric oxide synthase (NOS), spatially confined in specific intracellular compartments in cardiac cells, have distinct roles in the regulation of contractility in pathophysiological situations. Recently, evidence has emerged that implicates NOS in modulating myocardial remodelling during cardiac stress, including after ischaemic insults. As long as they remain in a coupled state the NOS mostly attenuate hypertrophic remodelling through both cGMP-dependent and independent mechanisms. We review the evidence provided from the phenotype of genetic mouse models as well as from in vitro cell experiments dissecting the signalling effectors involved in the NOS-mediated regulation that justify new therapeutic interventions on the NOS-cGMP axis to attenuate the development of heart failure.
三种一氧化氮合酶（NOS）同工型，在心脏细胞的特定细胞内隔室内空间上受限，在病理生理情况下对收缩性的调节中具有不同的作用。最近的证据表明，NOS 参与调节心脏应激时的心肌重塑，包括缺血性损伤后。只要它们保持偶联状态，NOS 主要通过 cGMP 依赖和非依赖机制来减弱肥厚性重塑。我们综述了遗传小鼠模型表型以及体外细胞实验提供的证据，这些实验剖析了涉及 NOS 介导的调节的信号效应物，这些证据证明了在 NOS-cGMP 轴上进行新的治疗干预以减弱心力衰竭发展的合理性。
