Combined inorganic nitrate/nitrite supplementation blunts α-mediated vasoconstriction during exercise in patients...

Patients with type 2 diabetes mellitus (T2DM) have reduced vasodilatory responses during exercise partially attributable to low nitric oxide (NO) levels. Low NO contributes to greater α-adrenergic mediated vasoconstriction in contracting skeletal muscle. We hypothesized boosting NO bioavailability via 8wks of active beetroot juice (BR_A, 4.03 mmol nitrate, 0.29 mmol nitrite, n = 19) improves hyperemia, via reduced α-mediated vasoconstriction, during handgrip exercise relative to nitrate/nitrite-depleted beetroot juice (BR_P, n = 18) in patients with T2DM.

Forearm blood flow (FBF) and vascular conductance (FVC) were calculated at rest and during handgrip exercise (20%max, 20contractions·min^-1). Phenylephrine (α₁-agonist) and dexmedetomidine (α₂-agonist) were infused intra-arterially during independent trials to determine the influence of α-mediated vasoconstriction on exercise hyperemia. Vasoconstriction was quantified as the percent-reduction in FVC during α-agonist infusion, relative to pre-infusion, as well as the absolute change in %FVC during exercise relative to the respective rest trial (magnitude of sympatholysis).

ΔFBF (156 ± 69 to 175 ± 73 ml min^-1) and ΔFVC (130 ± 54 to 156 ± 63 ml min^-1·100 mmHg^-1, both P < 0.05) during exercise were augmented following BR_A, but not BR_P (P = 0.96 and 0.51). Phenylephrine-induced vasoconstriction during exercise was blunted following BR_A (-17.1 ± 5.9 to -12.6 ± 3.1%, P < 0.01), but not BR_P (P = 0.58) supplementation; the magnitude of sympatholysis was unchanged by either (beverage-by-time P = 0.15). BR_A supplementation reduced dexmedetomidine-induced vasoconstriction during exercise (-23.3 ± 6.7 to -19.7 ± 5.2%) and improved the corresponding magnitude of sympatholysis (25.3 ± 11.4 to 34.4 ± 15.5%, both P < 0.05).

BR_A supplementation improves the hyperemic and vasodilatory responses to exercise in patients with T2DM which appears to be attributable to reduced α-adrenergic mediated vasoconstriction in contracting skeletal muscle.