Chronic Hindlimb Ischemia Impairs Functional Vasodilation and Vascular Reactivity in Mouse Feed Arteries

Abstract

Vasodilation of lower leg arterioles is impaired in animal models of chronic peripheral ischemia. In addition to arterioles, feed arteries are a critical component of the vascular resistance network, accounting for as much as 50% of the pressure drop across the arterial circulation. Despite the critical importance of feed arteries in blood flow control, the impact of ischemia on feed artery vascular reactivity is unknown. At 14 days following unilateral resection of the femoral–saphenous artery–vein pair, functional vasodilation of the profunda femoris artery was severely impaired, 11 ± 9 versus 152 ± 22%. Although endothelial and smooth muscle-dependent vasodilation were both impaired in ischemic arteries compared to control arteries (Ach: 40 ± 14 versus 81 ± 11%, SNP: 43 ± 12 versus and 85 ± 11%), the responses to acetylcholine and sodium nitroprusside were similar, implicating impaired smooth muscle-dependent vasodilation. Conversely, vasoconstriction responses to norepinephrine were not different between ischemic and control arteries, −68 ± 3 versus −66 ± 3%, indicating that smooth muscle cells were functional following the ischemic insult. Finally, maximal dilation responses to acetylcholine, ex vivo, were significantly impaired in the ischemic artery compared to control, 71 ± 9 versus 97 ± 2%, despite a similar generation of myogenic tone to the same intravascular pressure (80 mmHg). These data indicate that ischemia impairs feed artery vasodilation by impairing the responsiveness of the vascular wall to vasodilating stimuli. Future studies to examine the mechanistic basis for the impact of ischemia on vascular reactivity or treatment strategies to improve vascular reactivity following ischemia could provide the foundation for an alternative therapeutic paradigm for peripheral arterial occlusive disease.

Arterialized collateral capillaries progress from nonreactive to capable of increasing perfusion in an ischemic arteriolar tree

“…It is clear that vasodilation is impaired in both distal intramuscular arterioles (ie orders 3 and 4) and extraparenchymal muscular feed arteries in the ischemic zone, but the impact of arterial occlusion on collateral reactivity is poorly described. Consistent with clinical observations, collateral‐dependent hyperemia (increase in blood flow with muscle contraction) to skeletal muscle is reduced following arterial occlusion in several species .…”

Netrin-1 with stem cells promote angiogenesis in limb ischemic rats

“…The improvements of the muscular function are very important to ASO patients, ischemia and hypoxia could reduce the number of muscle fibers [19], and impair the vascular reactivity for functional vasodilation [20]. Chronic ischemia would significantly impair vasodilation in not only intramuscular arterioles [21] but also feed arteries [20].…”

“…Chronic ischemia would significantly impair vasodilation in not only intramuscular arterioles [21] but also feed arteries [20]. It could also cause mitochondrial dysfunction and oxidative damage, the respiratory activities of electron transport chain complexes I, III, and IV were significantly reduced in fibers of ischemic muscle [22].…”

Vascular Reactivity in Newly-Formed and Mature Arterialized Collateral Capillaries

“…Specifically, chronic ischemia due to peripheral arterial occlusive disease (PAOD) impairs vasodilation in the limb skeletal muscles (Figure 1) (4,9). In 2012, approximately 8 million Americans had PAOD, a number that has been Figure 1.…”

“…Ischemia-an insufficient blood supply to tissue-impairs arterial function in the microcirculation (9). Specifically, chronic ischemia due to peripheral arterial occlusive disease (PAOD) impairs vasodilation in the limb skeletal muscles (Figure 1) (4,9).…”