Abstract

A characteristic of peripheral vascular disease (PVD) in the metabolic syndrome (MS) is impaired skeletal muscle perfusion:demand matching, with increased adrenergic tone being a contributing element. However, despite increases in bulk perfusion to contracting muscle following adrenoreceptor blockade, fatigue resistance remains poor unless endothelial function is restored by treatment with antioxidants. Given that antioxidant treatment alone improves neither active hyperemia nor muscle fatigue, these observations suggest that additional processes are involved beyond simple bulk perfusion. Using in situ cremaster muscle, we determined that spatial perfusion heterogeneity at bifurcations was elevated in obese Zucker rats (OZR) vs. control and this pattern was repeated at multiple successive bifurcations in the network. The increased spatial heterogeneity was not compensated for via temporal activity, as perfusion distribution at bifurcations was less labile in OZR vs. control. Intravascular tracer washout (albumin) revealed an increased heterogeneity at the network level of resolution, correctable following adrenoreceptor blockade. These observations suggest that a critical component of PVD in MS is a shift in the spatio‐temporal distribution of perfusion at bifurcations in skeletal muscle and that only interventions that improve this will have a beneficial impact on tissue performance.

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