Nitric oxide (NO) plays a pivotal role in the maintenance of cardiovascular homeostasis. A reduction in the bioavailability of endogenous NO, manifest as a decrease in the production and/or impaired signaling, is associated with many cardiovascular diseases including hypertension, atherosclerosis, stroke and heart failure. There is substantial evidence that reactive oxygen species (ROS), generated predominantly from NADPH oxidases (Nox), are responsible for the reduced NO bioavailability in vascular and cardiac pathologies. ROS can compromise NO function via a direct inactivation of NO, together with a reduction in NO synthesis and oxidation of its receptor, soluble guanylyl cyclase. Whilst nitrovasodilators are administered to compensate for the ROS-mediated loss in NO bioactivity, their clinical utility is limited due to the development of tolerance and resistance and systemic hypotension. Moreover, efforts to directly scavenge ROS with antioxidants has had limited clinical efficacy. This review outlines the therapeutic utility of NO-based therapeutics in cardiovascular diseases and describes the source and impact of ROS in these pathologies, with particular focus on the interaction with NO. Future therapeutic approaches in the treatment of cardiovascular diseases are highlighted with a focus on nitroxyl (HNO) donors as an alternative to traditional NO donors and the development of novel Nox inhibitors.

一氧化氮（NO）在维持心血管稳态中起着关键作用。内源性NO的生物利用度降低表现为产生减少和/或信号传导受损，与许多心血管疾病有关，包括高血压，动脉粥样硬化，中风和心力衰竭。有大量证据表明，主要由NADPH氧化酶（Nox）产生的活性氧（ROS）导致血管和心脏病理中NO生物利用度降低。ROS可以通过NO的直接失活，以及NO合成的减少和其受体可溶性鸟苷酸环化酶的氧化而损害NO的功能。给予硝化舒张剂以补偿ROS介导的NO生物活性损失，由于耐受性和耐药性以及全身性低血压的发展，其临床应用受到限制。而且，用抗氧化剂直接清除ROS的努力已经限制了临床疗效。这篇综述概述了基于NO的疗法在心血管疾病中的治疗作用，并描述了ROS在这些病理中的来源和影响，尤其着重于与NO的相互作用。重点介绍了未来的心血管疾病治疗方法，重点是硝化（HNO）供体替代传统NO供体，并开发了新型NOx抑制剂。这篇综述概述了基于NO的疗法在心血管疾病中的治疗作用，并描述了ROS在这些病理中的来源和影响，特别着重于与NO的相互作用。重点介绍了未来的心血管疾病治疗方法，重点是将硝酰（HNO）供体替代传统的NO供体，并开发出新型的NOx抑制剂。这篇综述概述了基于NO的疗法在心血管疾病中的治疗作用，并描述了ROS在这些病理中的来源和影响，尤其着重于与NO的相互作用。重点介绍了未来的心血管疾病治疗方法，重点是硝化（HNO）供体替代传统NO供体，并开发了新型NOx抑制剂。