DECREASED TEMPORAL ACTIVITY AT MICROVASCULAR BIFURCATIONS EXACERBATES PERFUSION HETEROGENEITY IN SKELETAL MUSCLE IN THE METABOLIC SYNDROME

Abstract

We have demonstrated that peripheral vascular disease (PVD) in obese Zucker rats (OZR) is due to increased perfusion heterogeneity at successive microvascular bifurcations. This increased heterogeneity (γ) is longitudinally present in the microvascular network, but reflects differential contributions and effects of adrenergic constriction, elevated ROS and increased TxA2 production. The cumulative impact of increased γ is a more heterogeneous distribution of perfusion between terminal arterioles, leading to greater tissue ischemia. However, increased temporal switching at bifurcations should compensate for the increased γ, and minimize perfusion impairments. In cremaster muscle, we determined that temporal activity (the cumulative sum of absolute differences between successive values of γ, taken every 15 seconds for 5 minutes) was lower in OZR than controls, and this difference was present in both proximal (1A‐2A) and distal (3A‐4A) bifurcations. While adrenoreceptor blockade (phentolamine) improved outcomes proximally in OZR, this was without impact in the distal microcirculation, where only interventions against ROS (TEMPOL) and TxA2 (SQ‐29548) were effective. These data suggest that reduced temporal activity at microvascular bifurcations in OZR accentuates the effects of increased γ, exacerbating perfusion‐based elements underlying PVD. (NIH RR2465AR, T32 HL90610, AHA 0740129N)