| Summary: | Teleost fish are often regarded with interest for the remarkable ability of several species to tolerate even dramatic stresses, either internal or external, as in the case of fluctuations in O<sub>2</sub> availability and temperature regimes. These events are naturally experienced by many fish species under different time scales, but they are now exacerbated by growing environmental changes. This further challenges the intrinsic ability of animals to cope with stress. The heart is crucial for the stress response, since a proper modulation of the cardiac function allows blood perfusion to the whole organism, particularly to respiratory organs and the brain. In cardiac cells, key signalling pathways are activated for maintaining molecular equilibrium, thus improving stress tolerance. In fish, the nitric oxide synthase (NOS)/nitric oxide (NO) system is fundamental for modulating the basal cardiac performance and is involved in the control of many adaptive responses to stress, including those related to variations in O<sub>2</sub> and thermal regimes. In this review, we aim to illustrate, by integrating the classic and novel literature, the current knowledge on the NOS/NO system as a crucial component of the cardiac molecular mechanisms that sustain stress tolerance and adaptation, thus providing some species, such as tolerant cyprinids, with a high resistance to stress.
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