Nitric oxide synthases, S-nitrosylation and cardiovascular health: from molecular mechanisms to therapeutic opportunities (review).

The understanding of nitric oxide (NO) signaling has grown substantially since the identification of endothelial derived relaxing factor (EDRF). NO has emerged as a ubiquitous signaling molecule involved in diverse physiological and pathological processes. Perhaps the most significant function, independent of EDRF, is that of NO signaling mediated locally in signaling modules rather than relying upon diffusion. In this context, NO modulates protein function via direct post‑translational modification of cysteine residues. This review explores NO signaling and related reactive nitrogen species involved in the regulation of the cardiovascular system. A critical concept in the understanding of NO signaling is that of the nitroso‑redox balance. Reactive nitrogen species bioactivity is fundamentally linked to the production of reactive oxygen species. This interaction occurs at the chemical, enzymatic and signaling effector levels. Furthermore, the nitroso‑redox equilibrium is in a delicate balance, involving the cross‑talk between NO and oxygen‑derived species signaling systems, including NADPH oxidases and xanthine oxidase.