Changes in Vascular Nitrite and FeNO Following Acute Traffic Pollution Exposure With and Without Oral Nitrate Prophylaxis via Beet Juice
Authors: Kipen Howard M , Laumbach Robert J , Chaudhry Aisha , Truong Thu , Black Kathleen , Gow Andrew 
Published: November 2023

Background

Circulating NO2‐represents both a marker of endothelial function and a source of NO during hypoxia. Previously we have shown that healthy subjects display increased plasma NO2‐ in response to an ischemic stimulus and that this increase can be abolished by 2 hours of traffic related air pollution (TRAP), the same time frame by which TRAP exposure is epidemiologically associated with acute adverse outcomes such as MI. We have been exploring underlying mechanisms by which such acute effects of air pollution might occur, with a goal of being able to prevent or mitigate them. Dietary inorganic nitrates enter an enterosalivary circuit in which salivary gland bacteria reduce NO3‐ to NO2‐. This circulating NO2‐ is reduced in hypoxic environments to NO resulting in vasorelaxation. Beetroot is high in inorganic NO3‐. We investigated whether beetroot juice (BJ) can be used to supplement circulating NO2‐ levels, affect blood pressure response, and potentially alter the hypoxia response following exposure to TRAP.

Methods

20 male and female healthy volunteers participated in a randomized, placebo‐controlled, crossover study of whether BJ could ameliorate the oxidant effects of exposure to TRAP. Volunteers were randomized to receive 500ml of BJ (20 mM NO3‐) or orange juice (OJ, 0.001 mM NO3‐) on their first visit and the other on a second visit one week later. Before and after each ride, blood pressure, FeNO (NIOX MINO), and plasma NO2‐ concentration, and the change in plasma NO2‐ in response to a 5 min ischemic forearm stimulus were measured. Plasma NO2‐ was measured by chemical reduction chemiluminesence using a Sievers NOA. Following before‐ride plasma sampling, subjects consumed the juice and were driven on a 2 hour rush‐hour car ride in the truck lanes of the New Jersey Turnpike.

Results

Prior to the rides/juice, baseline circulating NO2‐ was 186 ±159 nM. The NO2‐concentration fell to 140±152 nM after the OJ ride (NS), whereas, even in the face of oxidant TRAP exposure it rose to 403±315 nM following the BJ/ride. Confirming systemic delivery of the NO2‐, the BJ/ride increased FeNO from 18.3 ppb to 29.6 ppb (p<0.0001), with a smaller increase during the OJ/ride (17.9 to 19.8 ppb; p=0.027). Systolic blood pressure rose an average of 1.5 mm Hg (NS) following the OJ rides, and this was reduced to a rise of 0.23 mm Hg (NS) following BJ rides. The change in hyperemic response (before to after the ride) was greater for BJ (38 nM) than for OJ (7 nM), but the difference was not significant as there was considerable variability in the response to both TRAP and BJ (σ=233 nM).

Conclusions

These data suggest that BJ can effectively supplement circulating NO2‐, despite exogenous oxidative stress from TRAP, representing a nutritional mechanism for supporting endothelial function. BJ also increased delivery of NO2‐ to the airways. We speculate that the increase in FeNO following OJ represents TRAP‐induced airway inflammation. Further investigations of prevention of a TRAP effect by BJ will need to incorporate a physiologic measure of endothelial function such as brachial artery ultrasound or peripheral arterial tonometry.

Support or Funding Information

This study was supported by the NIEHS P30 Center for Environmental Exposures and Disease ES005022