Modulation of rat skeletal muscle microvascular O2 pressure via KATP channel inhibition following the onset of contractions

•Vascular ATP-sensitive K+ (KATP) channel activation enhances exercise-induced hyperemia.•We examined the effect of KATP channel inhibition via glibenclamide on microvascular O2 driving pressure (PO2mv) kinetics following the onset of contractions.•Glibenclamide caused an undershoot of PO2mv, nearly doubled the time to reach the contracting steady-state and reduced the overall mean PO2mv.•This effect raises the question of whether muscle vascular KATP channel dysfunction underlies, in part, the clinical manifestations (e.g., exercise intolerance) associated with the use of sulphonylureas in the treatment of diabetes mellitus.

Vascular hyperpolarization mediated, in part, by the ATP-sensitive K+ (KATP) channel contributes to exercise-induced increases in skeletal muscle O2 delivery. We hypothesized that KATP channel inhibition via glibenclamide (GLI) would speed the fall of microvascular O2 driving pressure (PO2mv; set by the O2 delivery-O2 utilization ratio), during muscle contractions. Spinotrapezius muscle PO2mv (phosphorescence quenching) was measured in 12 adult Sprague Dawley rats during 180 s of 1-Hz twitch contractions (∼6 V) under control and GLI (5 mg/kg) conditions. The total mean PO2mv response time was greater with GLI (i.e., slowed; control: 42.0 ± 14.2, GLI: 79.5 ± 14.7 s, p < 0.05). A clear undershoot of the contracting steady-state PO2mv was evident with GLI (15.6 ± 5.3%, p < 0.05) but not control (2.3 ± 1.6%, p > 0.05). This indicates that KATP channel inhibition does not speed PO2mv kinetics per se during small muscle mass contraction. However, it does induce a transient mismatch of O2 delivery-O2 utilization, lowers PO2mv, and delays attainment of the contracting steady-state.