Contraction-evoked vasodilation and functional hyperaemia are compromised in branching skeletal muscle arterioles of young pre-diabetic mice

Abstract

Aim: To investigate the effects of pre-diabetes on microvascular network function in contracting skeletal muscle. We hypothesized that pre-diabetes compromises contraction-evoked vasodilation of branching second-order (2A), third-order (3A) and fourth-order (4A) arterioles, where distal arterioles would be affected the greatest.

Methods: Intravital video microscopy was used to measure arteriolar diameter (in 2A, 3A and 4A) and blood flow (in 2A and 3A) changes to electrical field stimulation of the gluteus maximus muscle in pre-diabetic (The Pound Mouse, PD) and control (c57bl6, CTRL) mice.

Results: Baseline diameter and blood flow were similar between groups (2A: ~20 μm, 3A: ~14 μm and 4A: ~8 μm; 2A: ~1 nL s(-1) and 3A: ~0.5 nL s(-1) ). Single tetanic contraction (100 Hz; 200, 400, 800 ms duration) evoked rapid-onset vasodilation (ROV) and blood flow responses that were blunted by ~50% and up to 81%, respectively, in PD vs. CTRL (P < 0.05). The magnitude of ROV was up to 2-fold greater at distal arterioles (3A and 4A) vs. proximal arterioles (2A) in CTRL; however, in PD, ROV of only 4A was greater than 2A (P < 0.05). Rhythmic contraction (2 and 8 Hz, 30 s) evoked vasodilatory and blood flow responses that were also attenuated by ~50% and up to 71%, respectively, in PD vs. CTRL (P < 0.05). The magnitude of vasodilatory responses to rhythmic contraction was also up to 2.5-fold greater at 4A vs. 2A in CTRL; however spatial differences in vasodilation across arteriolar branch orders was disrupted in PD.

Conclusions: Arteriolar dysregulation in pre-diabetes causes deficits in contraction-evoked dilation and blood flow, where greatest deficits occur at distal arterioles.

Keywords: blood flow; diabetes; exercise; functional vasodilation; microcirculation; skeletal muscle.