Abstract 504: Vulnerability of Conducted Vasomotor Response to Ischemia-Reperfusion Injury
Evidence suggests that ischemia-reperfusion injury (I/R) has a detrimental effect on vascular function. However, the effect of I/R on communication of vasomotor signals remains elusive. To investigate the effect of I/R on vascular communication, local I/R was produced in the hamster cheek pouch by occlusion of the cheek pouch pedicle for 30 min, followed by reperfusion for 60 min. Vascular communication was tested through conducted vasomotor responses from methacholine, and adenosine (microapplied to the arteriole, maximum diameter 30 – 60 μm). The local and conducted dilation to methacholine and adenosine were inhibited by I/R. In contrast, the local and conducted vasomotor contraction to phenylephrine was not altered by I/R. The local dilatory responses to KATP channel activator, cromakalim, and to guanylate cyclase activator, sodium nitroprusside, were also not altered after I/R, indicating the intact function of vascular smooth muscle. Vascular network responses initiated by tissue adenosine (injected 500 micron away from the arteriole) or electrical stimulation of nerves (in the cheek pouch tissue) causes remote arteriolar dilations (up to 500 and 1000 μm upstream) and were inhibited by local anesthetic bupivacaine (100 μM) and CGRP receptor inhibitor, CGRP8–37. I/R impaired the remote dilatory responses to tissue adenosine and electrical stimulation similar to that caused by neural inhibition. Interestingly, the local dilatory response to CGRP was not changed albeit the arteriolar dilatory response to chemical stimulation of CGRP sensory nerve with capsaicin was attenuated after I/R, suggesting a specific impairment of CGRP sensory nerves but not the vascular CGRP receptor. These results indicate that vascular communication is vulnerable to I/R and it is likely dysfunction of CGRP neural network leading to the uncoordinated vascular communication of various vasomotor responses.