The acute effects of dietary nitrate supplementation on postmenopausal endothelial resistance to ischemia reperfusion injury: a randomized, placebo-controlled, double blind, crossover clinical trial

Postmenopausal cardiovascular health is a critical determinant of longevity. Consumption of beetroot juice (BR) and other nitrate-rich foods is a safe, effective non-pharmaceutical intervention to increase systemic bioavailability of the vasoprotective molecule, nitric oxide, through the exogenous nitrate (NO₃ ⁻)-nitrite (NO₂ ⁻)-nitric oxide (NO) pathway. We hypothesized that a single dose of nitrate-rich beetroot juice (BRnitrate 600 mg NO₃ ⁻/140 mL, BRplacebo ∼ 0 mg/140 mL) would improve resting endothelial function and resistance to ischemia-reperfusion (IR) injury to a greater extent in early-postmenopausal (1-6 years following their final menstrual period (FMP), n = 12) compared to late-postmenopausal (6+ years after FMP, n = 12) women. Analyses with general linear models revealed a significant (p < 0.05) time*treatment interaction effect for brachial artery adjusted flow-mediated dilation (FMD). Pairwise comparisons revealed that adjusted FMD was significantly lower following IR-injury in comparison to all other time points with BRplacebo (early FMD 2.51 ± 1.18%, late FMD 1.30 ± 1.10, p < 0.001) and was lower than post-IR with BRnitrate (early FMD 3.84 ± 1.21%, late FMD 3.21 ± 1.13%, p = 0.014). A single dose of BRnitrate significantly increased resting macrovascular function in the late postmenopausal group only (p = 0.005). Considering the postmenopausal stage-dependent variations in endothelial responsiveness to dietary nitrate, we predict differing mechanisms underpin macrovascular protection against IR injury.