Acute effects of hydrogen peroxide on skeletal muscle microvascular oxygenation from rest to contractions

Reactive oxygen species, such as hydrogen peroxide (H2O2), exert a critical regulatory role on skeletal muscle function. Whether acute increases in H2O2 modulate muscle microvascular O2 delivery-utilization (Q̇o2/V̇o2) matching [i.e., microvascular partial pressure of O2 (PmvO2)] at rest and following the onset of contractions is unknown. The hypothesis was tested that H2O2 treatment (exogenous H2O2) would enhance PmvO2 and slow PmvO2 kinetics during contractions compared with control. Anesthetized, healthy young Sprague-Dawley rats had their spinotrapezius muscles either exposed for measurement of blood flow (and therefore Q̇o2), V̇o2, and PmvO2, or exteriorized for measurement of force production. Electrically stimulated twitch contractions (1 Hz, ∼7 V, 2-ms pulse duration, 3 min) were evoked following acute superfusion with Krebs-Henseleit (control) and H2O2 (100 μM). Relative to control, H2O2 treatment elicited disproportionate increases in Q̇o2 and V̇o2 that elevated PmvO2 at rest and throughout contractions and slowed overall PmvO2 kinetics (i.e., ∼85% slower mean response time; P < 0.05). Accordingly, H2O2 resulted in ∼33% greater overall PmvO2, as assessed by the area under the PmvO2 curve ( P < 0.05). Muscle force production was not altered with H2O2 treatment ( P > 0.05), evidencing reduced economy during contractions (∼40% decrease in the force/V̇o2 relationship; P < 0.05). These findings indicate that, although increasing the driving force for blood-myocyte O2 flux (i.e., PmvO2), transient elevations in H2O2 impair skeletal muscle function (i.e., reduced economy during contractions), which mechanistically may underlie, in part, the reduced exercise tolerance in conditions associated with oxidative stress.