Acute blood pressure lowering, vasoprotective, and antiplatelet properties of dietary nitrate via bioconversion to nitrite

Abstract

Diets rich in fruits and vegetables reduce blood pressure (BP) and the risk of adverse cardiovascular events. However, the mechanisms of this effect have not been elucidated. Certain vegetables possess a high nitrate content, and we hypothesized that this might represent a source of vasoprotective nitric oxide via bioactivation. In healthy volunteers, approximately 3 hours after ingestion of a dietary nitrate load (beetroot juice 500 mL), BP was substantially reduced (Delta(max) -10.4/8 mm Hg); an effect that correlated with peak increases in plasma nitrite concentration. The dietary nitrate load also prevented endothelial dysfunction induced by an acute ischemic insult in the human forearm and significantly attenuated ex vivo platelet aggregation in response to collagen and ADP. Interruption of the enterosalivary conversion of nitrate to nitrite (facilitated by bacterial anaerobes situated on the surface of the tongue) prevented the rise in plasma nitrite, blocked the decrease in BP, and abolished the inhibitory effects on platelet aggregation, confirming that these vasoprotective effects were attributable to the activity of nitrite converted from the ingested nitrate. These findings suggest that dietary nitrate underlies the beneficial effects of a vegetable-rich diet and highlights the potential of a "natural" low cost approach for the treatment of cardiovascular disease.

Figure 1

The effect of beetroot juice on the plasma concentrations of (a) nitrate and (b) nitrate and the effects of spitting versus swallowing of saliva on plasma concentrations of (c) nitrate, (d) nitrite. Data expressed as mean±SEM. Significance shown as: ANOVA of curve of ^†††P<0.001 beetroot juice vs. control, ^†P<0.05 spitting vs. swallowing followed by ^‡P<0.001 Bonferroni post test of beetroot juice v control, *P<0.05, **P<0.01 Dunnett’s post test compared to baseline.

Figure 2

The effect of beetroot juice on the change from baseline in (a) systolic BP (, (b) diastolic BP, (c) heart rate, (d) correlation of change in BP with change in plasma nitrite concentration and (e) effect of spitting versus swallowing of saliva on changes in systolic BP following beetroot juice. Data expressed as mean ± SEM. Significance shown as: ^††P<0.01, ^†††P<0.001 ANOVA of curve of beetroot juice vs. control, ^‡P<0.05, ^‡‡P<0.01, ^‡‡‡P<0.001 Bonferroni post test of beetroot juice vs. control; ^†P<0.001 compared to control pre-I/R, ^‡P<0.05 compared to post-I/R with beetroot juice.

Figure 3

Flow mediated dilatation (FMD) in ischemia-reperfusion (I/R) in control and the effect of beetroot juice. Data expressed as mean±SEM. Significance shown as: ^†P<0.001 compared to control pre-I/R, ^‡P<0.05 compared to post-I/R with beetroot juice.

Figure 4

The fate of dietary nitrate, derived from consuming beetroot juice. Systemically absorbed nitrate is concentrated 10-fold in the salivary glands (Left hand panel) and undergoes an enterosalivary circulation where it is reduced to nitrite by bacterial nitrate reductases on the dorsal surface of the tongue, and swallowed into the stomach providing a source of systemically available nitrite/NO. Right hand panel- nitrite is transported in the arterial circulation to resistance vessels, where lower O₂ tension favors the reduction of nitrite to NO, causing vasodilatation, with consequent lowering of BP.