A single dose of dietary nitrate supplementation protects against endothelial ischemia–reperfusion injury in early postmenopausal women

The onset of menopause and accompanying changes to ovarian hormones often precedes endothelial dysfunction in women. In particular, accelerated impairments in macrovascular and microvascular function coincide with the loss of estrogen, as does impaired endothelial responses to ischemia–reperfusion (IR) injury. In healthy, early postmenopausal women (n = 12; 3.9 ± 1.5 years since menopause) we tested the hypothesis that acute dietary nitrate (NO⁻₃) supplementation would improve endothelial function and attenuate the magnitude of endothelial dysfunction following whole-arm IR in comparison with placebo. In this randomized, double-blind, placebo-controlled, crossover study we tested participants before and after NO⁻₃-rich (BR_nitrate)andNO⁻₃-depleted (BR_placebo) beetroot juice (BR) consumption, as well as following IR injury, and 15 min after IR to assess recovery. Analyses with repeated-measures general linear models revealed a condition × time interaction for brachial artery flow-mediated dilation (FMD; P = 0.04), and no interaction effect was found for the near-infrared spectroscopy-derived reperfusion slope (P = 0.86). Follow-up analysis showed a significant decline in FMD following IR injury with BR_placebo in comparison with all other timepoints (all, P < 0.05), while this decline was not present with BR_nitrate (all, P > 0.05). Our findings demonstrate that a single dose of dietary NO⁻₃ minimizes IR-induced macrovascular endothelial dysfunction in healthy, early postmenopausal women, but does not improve resting macrovascular and microvascular function. Trial registration number: NCT03644472. Novelty:_{In healthy, early postmenopausal women, a single dose of}⁻_NO3-rich BR can protect against IR-induced endothelial dysfunc-tion. This protection may be due to nitric oxide bioactivity during IR rather than improved endothelial function prior to the IR protocol per se.