The impact of outward remodeling on vasodilation in skeletal muscle resistance arteries

Abstract

Collateral enlargement following arterial occlusion is thought to rescue downstream tissues from severe ischemic insult in patients with ischemic disease, such as peripheral arterial occlusive disease. However, in animal models, collateral‐dependent hyperemia is reduced after arterial occlusion, suggesting that vasodilation may be impaired. Impaired vasodilation would compromise the effectiveness of collaterals, as ischemia occurs during periods of increased metabolic demand. To assess the impact of collateral enlargement on vasodilation in resistance arteries, we ligated the femoral arteries of young, otherwise healthy mice to induce outward remodeling in the collateral circuit. Outward remodeling transiently impairs functional vasodilation, which is reduced at day‐7 (62 ± 3% vs. 93 ± 10%, p < 0.05), but improves by day‐28 (101 ± 4% vs. 115 ± 10%). Vascular reactivity studies indicate the impaired vasodilation is due to impaired smooth muscle‐dependent responses during outward remodeling, as both endothelial‐ and smooth muscle‐dependent vasodilation is impaired at day‐7 (100 ± 16% vs. 149 ± 15%, p < 0.05 and 103 ± 15% vs. 125 ± 15%, p < 0.05, respectively), but not at day‐28 (136 ± 24% vs. 142 ± 20% and 146 ± 18% vs. 124 ± 10%). Studies examining the cellular mechanism of the day‐7 impairment and the impact of impaired vasodilation on hemodynamics are currently underway.