Impaired vascular reactivity following chronic ischemia in arteries of the mouse hindlimb

Abstract

Collateral‐dependent hyperemia is reduced following chronic ischemia, but the contribution of individual vessel reactivity is unknown. Further, it is not known what aspect of the complex ischemic injury response impacts vascular reactivity. To determine the impact of ischemia on vascular reactivity, we measured functional vasodilation in the muscular branch artery following resection of the femoral artery proximal to the muscular branch, which induces ischemia in the muscular branch artery. On day‐14 after surgery the diameter of the muscular branch was measured using side‐stream dark field (SDF) imaging intravital microscopy. At moderate intensity skeletal muscle contraction (1mA, 200μs, 8Hz, 90sec), functional vasodilation is reduced compared to the contralateral limb (10.84 ± 8.79% versus 151.70 ± 22.15% increase above baseline). Conversely, at high intensity skeletal muscle contraction (1mA, 500μs, 8Hz, 90sec), the initial vasodilation is not different from the contralateral limb, but the ischemic arteries are refractory to regaining their resting diameter. The control artery returned to baseline diameter within 10‐minutes following high‐intensity muscle contraction, while the ischemic artery did not return to baseline after 25 minutes. Further investigation is underway to determine if endothelial or smooth muscle dysfunction underlies this abnormal reactivity in ischemic arteries.