Relationships Between Changes In Nitric Oxide Biomarkers And Physiological Outcomes Following Dietary Nitrate Supplementation

Dietary nitrate (NO3-) supplementation can increase nitric oxide (NO) bioavailability and thus reduce blood pressure (BP) and enhance muscle contractile function in humans. It is currently unclear to what extent changes in key NO biomarkers (e.g., NO3-, nitrite (NO2-), S-nitrosothiols (RSNOs)) in plasma, whole blood (WB), red blood cells (RBC) and skeletal muscle contribute to the physiological benefits of dietary NO3- ingestion. PURPOSE: To investigate the relationships between changes in various NO biomarkers in different blood compartments and skeletal muscle and the physiological effects of dietary NO3- ingestion. METHODS: Using a randomized, double-blind crossover design, 12 participants consumed beetroot juice (BR) (~12.8 mmol NO3-) and placebo beetroot juice (PL) (~0.08 mmol NO3-) acutely and then chronically (for 2 weeks). Resting BP was assessed, blood and skeletal muscle samples were collected, and 10 maximal voluntary isometric contractions of the knee extensors were performed at 2.5-3 hours following BR ingestion on day 1 and day 14. Two-way repeated measures ANOVA was used to assess the differences in resting BP and muscle contractile function between conditions (PL vs BR) and across time (acute vs chronic). The relationships between changes in NO biomarkers and changes in resting BP and muscle contractile function were assessed with Pearson or Spearman correlation coefficient. RESULTS: Diastolic blood pressure (DBP) was significantly reduced (-2 ± 3 mmHg, P = 0.03) following acute BR ingestion, and this was correlated with the increased WB [RSNOs] (rs = -0.61, P = 0.03). Although the absolute rate of torque development (RTD) was not improved following acute BR ingestion, changes in RTD at 0-30 ms, 0-50 ms and 30-50 ms were significantly correlated with changes in RBC [RSNOs] (rs = 0.62-0.63, P < 0.05). Following 2 weeks BR ingestion, RTD at 0-30 ms (39 ± 57 N.m.s-1) and 0-50 ms (79 ± 99 N.m.s-1) were significantly improved (all P < 0.05). The improved RTD at 0-30 ms was correlated with the increased muscle [NO3-] (r = 0.64, P = 0.03). CONCLUSION: [RSNOs] in blood (WB and RBC), and [NO3-] in skeletal muscle, appear to be relevant biomarkers of NO bioavailability which mediate the reduction of BP and the enhanced muscle contractile function following acute and chronic dietary NO3- ingestion in humans. Chenguang Wei is supported by a studentship, jointly provided by the University of Exeter and China Scholarship Council.