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(Stroke. 1996;27:134-139.)
© 1996 American Heart Association, Inc.
Articles |
Ischemia Reduces CGRP-Induced Cerebral Vascular Dilation in Piglets
From the Department of Anatomy and Cell Biology, East Carolina University, Medical School, Greenville (T.M.L.), and the Departments of Physiology and Pharmacology (W.M., D.W.B.) and Pediatrics (R.A.E.), Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC; and the Department of Physiology, Albert Szent-Györgyi Medical University, Szeged, Hungary (F.B.).
Correspondence to Thomas M. Louis, PhD, Department of Anatomy and Cell Biology, East Carolina University, Medical School, Greenville, NC 27858.
Background and Purpose Effects of anoxic stress on cerebrovascular responses to calcitonin gene–related peptide (CGRP) have not been examined previously. We determined the effects of total global ischemia on cerebral arteriolar responses to CGRP in newborn pigs.
Methods Piglets were anesthetized and ventilated with a respirator. Pial arteriolar diameter was determined using a closed cranial window and intravital microscopy. Baseline arteriolar diameters ranged from 80 to 100 µm. Arteriolar responses to 10-9 and 10-8 mmol/L CGRP applied topically were 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. However, 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 hours, 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 other animals, we examined effects of pretreatment with indomethacin (5 mg/kg IV) on ischemia-induced decreases in arteriolar responses to CGRP. Indomethacin administration did not preserve arteriolar dilation to CGRP at 1 hour after ischemia, but responses were normal at 2 hours.
Conclusions Total global ischemia leads to prolonged attenuated dilator responses of cerebral arterioles to CGRP. In addition, indomethacin treatment alters effects of ischemia on CGRP-induced dilation.
Key Words: cerebral arteries • indomethacin • oxygen radical • prostaglandins • vasodilation • pigs
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