Dose-response relationship between dietary nitrate intake and nitric oxide congeners in various blood compartments and skeletal muscle: Differential effects on skeletal muscle torque and velocity

Abstract

Plasma nitrate (NO₃⁻) and nitrite (NO₂⁻) increase in a dose-dependent manner following NO₃⁻ ingestion. To explore if the same dose-response relationship applies to other nitric oxide (NO) congeners in different blood compartments and skeletal muscle, as well as the subsequent physiological responses, we provided 11 healthy participants with NO₃⁻ depleted beetroot juice (placebo), and beetroot juice (BR) containing 6.4, 12.8 and 19.2 mmol NO₃⁻ in a randomised, crossover design. Blood and muscle samples were collected, and resting blood pressure (BP) was assessed, before and at 2.5–3 h post-ingestion. Muscle contractile function was assessed using a 5-min all-out maximal voluntary isometric knee extension test at 3.5 h post-ingestion. We found that plasma and skeletal muscle [NO₃⁻], and whole blood S-nitrosothiols ([RSNOs]) increased dose-dependently, while plasma [NO₂⁻] did not increase further with doses above 6.4 mmol NO₃⁻. No significant increases in skeletal muscle [NO₂⁻] were found following ingestion of any of these doses. Resting BP was only reduced after ingestion of 19.2 mmol NO₃⁻. Mean peak torque and mean torque impulse during the first 10 muscle contractions were significantly enhanced following ingestion of both 12.8 mmol and 19.2 mmol NO₃⁻ compared to placebo, while the mean absolute rate of torque development (RTD) at 0–50 ms and 0–100 ms was significantly improved following ingestion of 6.4 mmol NO₃⁻ compared to placebo and 19.2 mmol NO₃⁻. Significant correlations were found between changes in red blood cell [RSNOs] and changes in absolute RTD at 0–50 ms (r_s = −0.70, P = 0.02) and 0–100 ms (r_s = −0.84, P < 0.01) following the ingestion of 6.4 mmol NO₃⁻. Our findings suggest that a high dose of 12.8 mmol NO₃⁻ is necessary to improve muscle contractile torque, while a lower dose of 6.4 mmol NO₃⁻ is sufficient to enhance muscle contractile velocity, at least for the type of exercise employed in the present study.