Oral Nitrate Increases Microvascular Reactivity and the Number of Visible Perfused Microvessels in Healthy Volunteers

Nitric oxide (NO) plays an important role in controlling microcirculatory function, but the effects of exogenous administration of nitrate (NO₃^-) on the microcirculation have not been well studied. We evaluated whether NO₃^- could influence the microvascular response to hypoxia in 17 healthy volunteers. We used a vascular occlusion test (VOT) to assess the response of near-infrared spectroscopy-derived indexes to hypoxic stress before and 2 h 15 min after oral administration of 800 mg potassium nitrate. We also monitored changes in the sublingual microcirculation using side-stream dark-field (SDF) video microscopy. The descending (7.3 [6.8-8.1] to 8.2 [7.9-9.8] %/min, p = 0.01) and ascending (201 [180-233] to 240 [197-285] %/min, p = 0.01) thenar oxygen saturation (StO₂) slopes were significantly greater during VOT after nitrate administration than before. Sublingual SDF measurements showed increases in the total number of visible perfused vessels (i.e., from 14.1 [13.2-15.5] to 16.3 [15.4-16.7] vessels/mm, p < 0.01) and in the number of visible perfused small vessels (i.e., from 12.2 [11.5-13.7] to 14.2 [13.5-15.3] vessels/mm, p < 0.01) after nitrate administration but no changes in the microvascular flow index or in the proportion of visible perfused vessels, which were already maximal at baseline. Oral administration of nitrate therefore significantly influenced the response to a hypoxic challenge, increasing the number of visible perfused vessels and thus possibly limiting the O₂ diffusion distance.