Mechanisms of the protective effects of nitrate and nitrite in cardiovascular and metabolic diseases.

Within the body, NO is produced by nitric oxide synthases via converting l-arginine to citrulline. Additionally, NO is also produced via the NOS-independent nitrate-nitrite-NO pathway. Unlike the classical pathway, the nitrate-nitrite-NO pathway is oxygen independent and viewed as a back-up function to ensure NO generation during ischaemia/hypoxia. Dietary nitrate and nitrite have emerged as substrates for endogenous NO generation and other bioactive nitrogen oxides with promising protective effects on cardiovascular and metabolic function. In brief, inorganic nitrate and nitrite can decrease blood pressure, protect against ischaemia-reperfusion injury, enhance endothelial function, inhibit platelet aggregation, modulate mitochondrial function and improve features of the metabolic syndrome. However, many questions regarding the specific mechanisms of these protective effects on cardiovascular and metabolic diseases remain unclear. In this review, we focus on nitrate/nitrite bioactivation, as well as the potential mechanisms for nitrate/nitrite-mediated effects on cardiovascular and metabolic diseases. Understanding how dietary nitrate and nitrite induce beneficial effect on cardiovascular and metabolic diseases could open up novel therapeutic opportunities in clinical practice.