ACCs mature into resistance vessels that regulate blood flow to the downstream tissue. Therefore, induction of mature ACCs may be a target for reducing ischemia in patients who lack collateral networks.
Native collateral vessels creates a natural bypass for blood flow around an arterial occlusion, potentially mitigating the effects of ischemic diseases, such as peripheral arterial occlusive disease in which arterial stenosis restricts blood flow to the limbs. Unfortunately, not all patients have robust collateral networks; however, animal models lacking native collaterals demonstrate the ability to adapt to the ischemic environment through arterialization of collateral capillaries, reperfusing the ischemic zone. Reactivity is important for normal muscle function in these developed vessels because increased metabolic demand is only satisfied when blood vessels can dilate to increase flow. Understanding cellular mechanisms behind impaired vasodilation is key to identifying potential therapeutic targets for improving reactivity. To assess vascular reactivity, the lateral cranial spinotrapezius feed artery was ligated 7 days prior to the application of endothelial‐dependent (acetylcholine, ACh) and endothelial‐independent (sodium nitroprusside, SNP) vasodilators. Although arterialized capillaries dilated significantly in response to ACh and SNP, dilation was impaired when compared to equivalent‐diameter terminal arterials on the sham side (19.0 ± 3.6% vs. 69.5 ± 14.0% and 20.0 ± 4.9% vs. 95.7 ± 9.2%, respectively). This impairment can be attributed to smooth muscle cell dysfunction because the responses to ACh and SNP are similar. To determine if other smooth muscle‐dependent vasodilatory pathways are also impaired, hydrogen sulfide and papaverine were applied using the same methods (31.3 ± 16.6% vs. 97.1 ± 16.2% and 49.0 ± 8.8% vs. 86.3 ± 6.1%). Future work will further characterize the signaling cascades described herein.
During ischemic events, natural bypass routes such as collateral arterioles can redirect blood flow to the ischemic zone. However, reperfusion of the ischemic arterial tree can also occur in animal models that lack arteriole collaterals, such as Balb/C mice. Collateral capillaries associated with the ischemic arterial tree enlarge and recruit smooth muscle cells in response to an increased pressure gradient. The arterialized collateral capillaries (ACC) must also be able to dilate and constrict in response to the changing metabolic needs of the tissue fed by them. By 21 days after the onset of ischemia, ACCs begin to dilate and constrict in response to physiological stimuli, however it has yet to be shown if the vasodilation of ACCs will increase blood flow in the ischemic arterial tree. To test whether vasodilation of the ACCs will increase blood flow in the ischemic arterial tree, we used laser speckle flowmetry at 21 days post‐ligation of the lateral cranial feed artery of the spinotrapezius muscle. We captured laser speckle images of the entire muscle to determine blood velocities at rest and after application of sodium nitroprusside (SNP). SNP increased blood velocity in the ischemic arterial tree by 60 ± 7% above res2ting velocity. Similarly, in unoperated vasculatures, blood velocity in arterial trees increased by 47 ± 5% above resting velocity. Comparable blood velocity increases between operated and unoperated vasculatures suggest that the ACCs are able to not only increase blood flow to the ischemic arterial tree, but also adequately respond to tissue metabolic demand. These results indicate that supporting the function of ACCs may be a potential therapeutic option for chronic ischemic diseases and their associated complications.
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