SELECTIVE IMPAIRMENT OF RESPONSE TO ACETYLCHOLINE AFTER ISCHEMIA REPERFUSION IN MICE/

Background and Purpose We previously reported that the endothelium-dep endent dilation of pial arterioles by either topical acetylcholine (AC h) or bradykinin (BK) was markedly inhibited after 10 minutes of near total ischemia after bilateral carotid occlusion. The present study te sts the responses after 10 minutes of reperfusion and investigates the effect of either oxygen or oxygen radical scavengers on the results. Methods Mice were subjected to bilateral carotid ligation or sham liga tion. Pial arteriolar diameters were monitored by an image-splitting t echnique at a craniotomy site. In separate studies, the responses to t opically suffused ACh, BK, or sodium nitroprusside (SNP) were tested b efore ischemia. After 10 minutes of ischemia and 10 minutes of reperfu sion, the response was assessed again. Sham-operated mice were observe d in each study. Cerebral blood flow was continuously monitored with a laser-Doppler technique. Additional separate studies were conducted a s follows: presence of superoxide dismutase plus catalase during ische mia and reperfusion, or in crease in the inspired oxygen (arterial oxy gen) and oxygen in suffusate. Results The response to ACh was signific antly impaired after 10 minutes of reperfusion. The responses to BK an d SNP were unaffected. Radical scavengers failed to influence the impa ired response to ACh. Elevations of arterial and suffusate oxygen leve ls to over 300 mm Hg failed to prevent the impairment. Conclusions Aft er 10 minutes of reperfusion, a selective impairment of the response t o ACh remains. The response to another endothelium-dependent dilator. BK, recovered, and the response to endothelium-independent SNP was una ffected. Because neither radical scavengers nor oxygen altered the out come with respect to ACh, I suggest that neither radical generation no r hypoxia accounts for the selective impairment of dilation by ACh. Ra ther, I hypothesize that reduced shear during ischemia diminishes the ability of the endothelium to synthesize and/or release the endotheliu m-derived relaxing factor for ACh. I hypothesize further that this imp aired release or synthesis persists throughout the 10-minute period of reperfusion.