Impaired microvascular control in contracting skeletal muscle in a murine model of prediabetes

Our group and others have shown that vascular dysfunction is associated with prediabetes and contributes to compromised modulation of blood flow in skeletal muscle. However, few studies have investigated the impact of prediabetes on microvascular function in contracting skeletal muscle. Thus, we sought to determine whether contraction‐evoked rapid onset vasodilation (ROV) is impaired in the gluteus maximus muscle of prediabetic mice (n=4, PD, Pound Mouse) compared to control C57Bl/6 mice (n=7, CTRL). Vascular responses of second order arterioles (2A) were assessed using intravital video microscopy following single tetanic (100Hz) contractions and 30s rhythmic contractions (2, 4, 8 Hz). Baseline luminal 2A diameter was greater in PD (26 ± 1 μm) compared to CTRL (22 ± 1 μm), however maximum diameter was similar (~30 μm, 10 μM SNP). The magnitude of ROV increased (from 4 to 14 μm) and was stimulus duration (100–1000 ms) dependent in CTRL, but not in PD. ROV in PD was attenuated by ~50% for 600–1000 ms tetanic contractions (P<0.05 vs. CTRL). 30s rhythmic contractions resulted in frequency‐dependent vasodilation in both groups, with no differences in magnitude. These data indicate that ROV is impaired in prediabetes, which may compromise exercise capacity. Support: NSERC.