Blunted temporal activity of microvascular perfusion heterogeneity in metabolic syndrome: a new attractor for peripheral vascular disease?

Abstract

A key outcome for peripheral vascular disease (PVD) is a progressive decay in skeletal muscle fatigue resistance with elevated metabolic demand. We have demonstrated that PVD in obese Zucker rats (OZR) is partially due to increased perfusion distribution heterogeneity (γ) at successive microvascular bifurcations, with its cumulative impact being an increasingly heterogeneous distribution of perfusion across terminal arterioles, leading to greater tissue ischemia. To minimize this outcome, a likely compensatory mechanism against increased γ should be an increased temporal switching at bifurcations to blunt downstream deficits. Using in situ cremaster muscle, we determined that temporal activity was lower in OZR than in LZR, and this difference was present in both proximal (1A‐2A) and distal (3A‐4A) arteriolar bifurcations. While adrenoreceptor blockade (phentolamine) improved temporal activity in 1A‐2A bifurcations in OZR, this was without impact in the distal microcirculation, where only interventions against oxidant stress (TEMPOL) and thromboxane A2 activity (SQ‐29548) were effective. Analysis of the attractor for γ indicated that it was elevated in OZR, and also exhibited a reduced range, suggesting that the ability of the microcirculation to respond to any challenge is highly restricted, and may represent the major contributor to the poor muscle performance in OZR.