The
metabolic syndrome is a clustering of risk factors of metabolic origin that increase the risk for
cardiovascular disease and
type 2 diabetes. A proposed central event in
metabolic syndrome is a decrease in the amount of bioavailable
nitric oxide (NO) from endothelial
NO synthase (eNOS). Recently, an alternative pathway for NO formation in mammals was described where inorganic
nitrate, a supposedly inert NO oxidation product and unwanted dietary constituent, is serially reduced to
nitrite and then NO and other bioactive
nitrogen oxides. Here we show that several features of
metabolic syndrome that develop in eNOS-deficient mice can be reversed by dietary supplementation with
sodium nitrate, in amounts similar to those derived from eNOS under normal conditions. In humans, this dose corresponds to a rich intake of vegetables, the dominant dietary
nitrate source.
Nitrate administration increased tissue and plasma levels of bioactive
nitrogen oxides. Moreover, chronic
nitrate treatment reduced visceral fat accumulation and circulating levels of
triglycerides and reversed the prediabetic phenotype in these animals. In rats, chronic
nitrate treatment reduced blood pressure and this effect was also present during NOS inhibition. Our results show that dietary
nitrate fuels a
nitrate-
nitrite-NO pathway that can partly compensate for disturbances in endogenous NO generation from eNOS. These findings may have implications for novel nutrition-based preventive and therapeutic strategies against
cardiovascular disease and
type 2 diabetes.