Does dietary nitrate say NO to cardiovascular ageing? Current evidence and implications for research

Abstract

CVD are characterised by a multi-factorial pathogenesis. Key pathogenetic steps in the development of CVD are the occurrence of endothelial dysfunction and formation of atherosclerotic lesions. Reduced nitric oxide (NO) bioavailability is a primary event in the initiation of the atherosclerotic cascade. NO is a free radical with multiple physiological functions including the regulation of vascular resistance, coagulation, immunity and oxidative metabolism. The synthesis of NO proceeds via two distinct pathways identified as enzymatic and non-enzymatic. The former involves the conversion of arginine into NO by the NO synthases, whilst the latter comprises a two-step reducing process converting inorganic nitrate $({\rm NO}_3^ - )$ into nitrite and subsequently NO.Inorganic ${\rm NO}_3^ - $ is present in water and food, particularly beetroot and green leafy vegetables. Several investigations have therefore used the non-enzymatic NO pathway as a target for nutritional supplementation (${\rm NO}_3^ - $ salts) or dietary interventions (high-${\rm NO}_3^ - $ foods) to increase NO bioavailability and impact on cardiovascular outcomes. Some studies have reported positive effects of dietary ${\rm NO}_3^ - $ on systolic blood pressure and endothelial function in patients with hypertension and chronic heart failure. Nevertheless, results have been inconsistent and the size of the effect appears to be declining in older individuals. Additionally, there is a paucity of studies for disorders such as diabetes, CHD and chronic kidney failure. Thus, whilst dietary ${\rm NO}_3^ - $ supplementation could represent an effective and viable strategy for the primary and secondary prevention of age-related cardiovascular and metabolic diseases, more large-scale, robust studies are awaited to confirm or refute this notion.