School of Physical Education and Sport, Laboratory of Biochemistry and Molecular Biology of the Exercise, University of Sao Paulo, Sao Paulo, Brazil.
Department of Exercise Physiology, King Saud University, Riyadh, Saudi Arabia.
Adv Exp Med Biol. 2017;1000:211-245. doi: 10.1007/978-981-10-4304-8_13.
Nitric oxide (NO) is a small molecule implicated in multiple signal transduction pathways thus contributing to the regulation of many cellular functions. The identification of NO synthase (NOS) isoforms and the subsequent characterization of the mechanisms of cell activation of the enzymes permitted the partial understanding of both the physiological and pathological processes. NO bioavailability plays an important role in the pathophysiology of cardiovascular disease and its reduction in endothelial cells is strictly associated to endothelial dysfunction which, in turn, correlates with cardiovascular mortality. Indeed, endothelial NO synthase (eNOS) has a key role in limiting cardiac dysfunction and remodeling in heart diseases, in part by decreasing myocyte hypertrophy. Conversely, exercise training is recommended to prevent and treat cardiovascular diseases-associated disorders at least by enhanced NO synthase activity and expression, and increased production of antioxidants, which prevents premature breakdown of NO. Exercise training may cause an improvement in endothelial function for both experimental animals and humans; Studies in both healthy subjects and patients with impaired NO-related vasorelaxation remarked exercise training ability to improve vascular structure and function and endothelial homeostasis. This chapter will briefly consider the importance of NO signaling in the maintenance of cardiovascular physiology, and discuss recent insights into the effect of exercise training on the signaling pathways that modulate NO synthesis and degradation in health and cardiovascular disease. In addition, we will highlight the molecular mechanisms via which microRNAs (miRs) target NO signaling in the cardiovascular system, and NO as a candidate molecule for development of new therapies.
一氧化氮（NO）是一种参与多种信号转导途径的小分子，因此有助于调节许多细胞功能。NO 合酶（NOS）同工型的鉴定以及随后对酶的细胞激活机制的特征描述，使我们对生理和病理过程有了部分的理解。NO 的生物利用度在心血管疾病的病理生理学中起着重要作用，内皮细胞中 NO 的减少与内皮功能障碍密切相关，而内皮功能障碍又与心血管死亡率相关。事实上，内皮型一氧化氮合酶（eNOS）在限制心脏病中的心肌功能障碍和重塑方面起着关键作用，部分原因是减少了心肌细胞肥大。相反，运动训练被推荐用于预防和治疗与心血管疾病相关的疾病，至少可以通过增强 NO 合酶活性和表达以及增加抗氧化剂的产生来防止 NO 的过早分解。运动训练可能会改善实验动物和人类的内皮功能；在健康受试者和 NO 相关血管舒张功能障碍患者的研究中，运动训练能够改善血管结构和功能以及内皮稳态的能力得到了证实。本章将简要讨论 NO 信号在维持心血管生理学中的重要性，并讨论最近关于运动训练对调节 NO 合成和降解的信号通路的影响的新见解，这些信号通路在健康和心血管疾病中。此外，我们将强调 microRNAs（miRs）靶向心血管系统中 NO 信号的分子机制，以及 NO 作为开发新疗法的候选分子。
