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 coincides 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 (NO3-) supplementation would improve endothelial function and attenuate the magnitude of endothelial dysfunction following whole-arm IR in comparison to placebo. In this randomized, double-blind, placebo-controlled, crossover study we tested participants before and after NO3–rich (BRnitrate) and NO3–depleted (BRplacebo) beetroot juice consumption, as well as following IR injury, and 15 minutes 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 NIRS-derived reperfusion slope (p=0.86). Follow up analysis showed a significant decline in FMD following IR injury with BRplacebo in comparison to all other timepoints (all, ptextless0.05), whilst this decline was not present with BRnitrate (all, ptextgreater0.05). Our findings demonstrate that a single dose of dietary NO3- minimizes IR-induced macrovascular endothelial dysfunction in healthy, early postmenopausal women, but does not improve resting macrovascular and microvascular function. Novelty: -In healthy, early postmenopausal women, a single dose of NO3–rich beetroot juice can protect against IR-induced endothelial dysfunction -This protection may be due to NO bioactivity during IR rather than improved endothelial function prior to IR

Applied Physiology, Nutrition, and Metabolism