ISCHEMIA REDUCES CGRP-INDUCED CEREBRAL VASCULAR DILATION IN PIGLETS

Background and Purpose Effects of anoxic stress on cerebrovascular res ponses to calcitonin gene-related peptide (CGRP) have not been examine d previously. We determined the effects of total global ischemia on ce rebral arteriolar responses to CGRP in newborn pigs. Methods Piglets w ere anesthetized and ventilated with a respirator. Pial arteriolar dia meter was determined using a closed cranial window and intravital micr oscopy. Baseline arteriolar diameters ranged from 80 to 100 mu m. Arte riolar responses to 10(-9) and 10(-8) mmol/L CGRP applied topically we re determined before and 1, 2, and 4 hours after a 10-minute period of total global ischemia. Ischemia was caused by increasing intracranial pressure. Results Before ischemia, CGRP dilated arterioles by 14+/-2% (n=6) and 24+/-3% (n=7) at 10(-9) and 10(-8) mmol/L, respectively. Ho wever, after ischemia, arteriolar responses to 10(-9) mmol/L CGRP were reduced at 1 hour to 4+/-1%, at 2 hours to 3+/-2%, and at 4 hours to 5+/-4% (P<.05 for all comparisons). Similarly, arteriolar responses to 10(-8) mmol/L CGRP were reduced to 5+/-2% at 1 hour, 5+/-2% at 2 hour s, and 10+/-6% at 4 hours (P<.05 for all comparisons). In time control animals, arteriolar responses to CGRP did not change over time. In ot her animals, we examined effects of pretreatment with indomethacin (5 mg/kg IV) on ischernia-induced decreases in arteriolar responses to CG RP. Indomethacin administration did not preserve arteriolar dilation t o CGRP at 1 hour after ischemia, but responses were normal at 2 hours. Conclusions Total global ischemia leads to prolonged attenuated dilat or responses of cerebral arterioles to CGRP. In addition, indomethacin treatment alters effects of ischemia on CGRP-induced dilation.