LAUSR

Air pollution is a major cause of cardiovascular and all-cause mortality. Disentangling the relative contributions of pollutants is challenging, as epidemiological data measuring exposure to one (eg, nitrogen dioxide [NO2]) is inevitably confounded by exposure to others (eg, particulate matter). Animal studies suggest that inhaled NO2 has the potential to increase plasma [nitrite] 1; a chemical originally considered to be physiologically inert before we found that its reduction to nitric oxide protects the myocardium against ischemia-reperfusion injury and lowers blood pressure in humans.2 We conducted an acute, randomized, controlled, crossover study to assess the impact of 90 minutes exposure to NO2 (from sitting next to a domestic gas cooker with gas hobs lit and uncovered) versus control (room air) on plasma [nitrite] (primary end point) and blood pressure (secondary end points) in 12 healthy participants. All underwent both interventions/visits (interval 7–108 days) in a computergenerated randomized order. Baseline characteristics (mean±SD): 26±4years, 10/12 female, body mass index 21.9±3.0 kg/m2, systolic blood pressure 113.8±7.9 mm Hg, diastolic blood pressure 72.8±5.7 mm Hg. The exposure phase was followed by a 90 minutes washout phase at background [NO2]. Participants fasted for 12 hours before each visit and received 250 mL low-nitrate water at time 0 h/1.5 h. The study was powered for a difference in plasma [nitrite] of 27±40 nmol/L on repeated-measures, 2-way ANOVA (α, 0.05 and β, 0.2) following D’Agostino-Pearson normalityconfirmation, with Sidak post-test (GraphPad Prism v8.2.1).3 The data that support the findings of this study are available from the corresponding author upon reasonable request. Relative to control, exposure increased ambient [NO2]: 276.3±38.5 versus 27.6±2.8 ppb (P<0.001). Plasma [nitrite] was increased through both the 90 minutes NO2 exposure and 90 minutes washout (P<0.001; Figure [A]). NO2 exposure decreased both systolic blood pressure and diastolic blood pressure (both P<0.001; Figure [B] and [C]). The largest decrease in systolic blood pressure relative to control occurred at 45 minutes (4.6 mm Hg [95% CI, 0.2–8.9]; P=0.032) and 90 minutes (5.5 mm Hg [95% CI, 1.2– 9.9]; P=0.005). The effect of NO2 on diastolic blood pressure was maximal at 45 minutes (5.7 mm Hg [95% CI, 0.9–10.5]; P=0.009). The temporal relationship between the increase in plasma [nitrite] and systolic blood pressure/diastolic blood pressure reduction (≈5 mm Hg) is consistent with studies investigating dietary nitrate.2 Furthermore, whilst the level of NO2 exposure (276.3±38.5 ppb) was ≈2.5-fold greater than recommended limits for exposure (eg, World Health Organization guideline 105 ppb 1-hour mean), it is less than that recorded adjacent to busy roads or in some domestic kitchens (≈2000 ppb).