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.

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 (rs = -0.70, P = 0.02) and 0-100 ms (rs = -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.