This review describes and summarizes the role of neuronal nitric oxide synthase (nNOS) on the central nervous system, particularly on brain regions such as the ventrolateral medulla (VLM) and the periaqueductal gray matter (PAG), and on blood vessels and the heart that are involved in the regulation and control of the cardiovascular system (CVS). Furthermore, we shall also review the functional aspects of nNOS during several physiological, pathophysiological, and clinical conditions such as exercise, pain, cerebral vascular accidents or stroke and hypertension. For example, during stroke, a cascade of molecular, neurochemical, and cellular changes occur that affect the nervous system as elicited by generation of free radicals and nitric oxide (NO) from vulnerable neurons, perioxide formation, superoxides, apoptosis, and the differential activation of three isoforms of nitric oxide synthases (NOSs), and can exert profound effects on the CVS. Neuronal NOS is one of the three isoforms of NOSs, the others being endothelial (eNOS) and inducible (iNOS) enzymes. Neuronal NOS is a critical homeostatic component of the CVS and plays an important role in regulation of different systems and disease process including nociception. The functional and physiological roles of NO and nNOS are described at the beginning of this review. We also elaborate the structure, gene, domain, and regulation of the nNOS protein. Both inhibitory and excitatory role of nNOS on the sympathetic autonomic nervous system (SANS) and parasympathetic autonomic nervous system (PANS) as mediated via different neurotransmitters/signal transduction processes will be explored, particularly its effects on the CVS. Because the VLM plays a crucial function in cardiovascular homeostatic mechanisms, the neuroanatomy and cardiovascular regulation of the VLM will be discussed in conjunction with the actions of nNOS. Thereafter, we shall discuss the up-to-date developments that are related to the interaction between nNOS and cardiovascular diseases such as hypertension and stroke. Finally, we shall focus on the role of nNOS, particularly within the PAG in cardiovascular regulation and neurotransmission during different types of pain stimulus. Overall, this review focuses on our current understanding of the nNOS protein, and provides further insights on how nNOS modulates, regulates, and controls cardiovascular function during both physiological activity such as exercise, and pathophysiological conditions such as stroke and hypertension.

这篇综述描述和总结了神经元一氧化氮合酶 (nNOS) 对中枢神经系统的作用，特别是对大脑区域如延髓腹外侧 (VLM) 和导水管周围灰质 (PAG) 以及血管和心脏的作用。参与心血管系统（CVS）的调节和控制。此外，我们还将回顾 nNOS 在几种生理、病理生理和临床条件下的功能方面，例如运动、疼痛、脑血管意外或中风和高血压。例如，在中风期间，会发生一系列影响神经系统的分子、神经化学和细胞变化，这些变化是由易受伤害的神经元产生自由基和一氧化氮 (NO)、过氧化物形成、超氧化物、细胞凋亡、以及一氧化氮合酶 (NOS) 的三种异构体的差异激活，并且可以对 CVS 产生深远的影响。神经元 NOS 是 NOS 的三种同种型之一，其他是内皮酶 (eNOS) 和诱导型 (iNOS) 酶。神经元 NOS 是 CVS 的关键稳态成分，在调节不同系统和疾病过程（包括伤害感受）中起重要作用。NO 和 nNOS 的功能和生理作用在本综述的开头进行了描述。我们还详细阐述了 nNOS 蛋白的结构、基因、结构域和调控。将探讨通过不同神经递质/信号转导过程介导的 nNOS 对交感自主神经系统 (SANS) 和副交感自主神经系统 (PANS) 的抑制和兴奋作用，特别是它对 CVS 的影响。由于 VLM 在心血管稳态机制中起着至关重要的作用，因此将结合 nNOS 的作用讨论 VLM 的神经解剖学和心血管调节。此后，我们将讨论与 nNOS 与心血管疾病（如高血压和中风）之间的相互作用相关的最新发展。最后，我们将关注 nNOS 的作用，特别是在 PAG 在不同类型的疼痛刺激期间在心血管调节和神经传递中的作用。总体而言，这篇综述重点介绍了我们目前对 nNOS 蛋白的理解，并提供了关于 nNOS 如何在运动等生理活动期间调节、调节和控制心血管功能的进一步见解，