Role of pacap in the relationship between camp and opioids in hypoxia-induced pial artery vasodilation. Wilderman, M. J., and W. M. Armstead. Departments of Anesthesia and Pharmacology, The University of Pennsylvania and The Children's Hospital of Philadelphia, Philadelphia, PA 19104-4399
APStracts 3:0430H, 1996.
The opioids methionine enkephalin and leucine enkephalin contribute to hypoxic pial artery dilation in the newborn pig and cAMP analogues have been shown to elevate CSF opioid concentration. The present study was designed to investigate the contribution of cAMP to hypoxic dilation and to determine if an endogenous activator of adenylate cyclase, pituitary adenylate cyclase activating peptide (PACAP), could modulate cAMP-induced release of opioids to contribute to hypoxic pial dilation in piglets equipped with closed cranial windows. An [alpha] level of p<0.05 was considered significant in all statistical tests. Moderate and severe hypoxia (PO2 nearly equal to 35 and 25mm Hg) induced pial artery dilation that was attenuated by Rp 8-Bromo cAMPs, a cAMP antagonist (24+/-1 and 36+/-2 vs. 21+/-1 and 30+/-1%, for moderate and 34+/-1 and 46+/-2 vs. 24+/-1 and 32+/-1%, for severe hypoxia, respectively before and after Rp 8 -Bromo cAMPs). These responses were associated with increased CSF cAMP (1046+/-25, 1366+/-28 and 1735+/-47 fmol/ml for control, moderate, and severe hypoxia respectively). Hypoxic pial dilation was also accompanied by an increase in CSF methionine enkephalin (1101+/-62, 3283+/-119, and 3835+/-129 pg/ml for control, moderate and severe hypoxia, respectively). Hypoxic dilation additionally increased CSF PACAP (1727+/-86, 2268+/-157, and 7980+/-238 pg/ml for control, moderate, and severe hypoxia). PACAP (10-8, 10-6 M) elicited pial dilation that was associated with increased CSF cAMP and blunted by Rp 8-Bromo cAMPs. PACAP induced dilation was also accompanied by increases in the opioid methionine enkephalin (1059+/-23, 1483+/-34, and 2108+/-77 pg/ml for control, 10-8 and 10-6 M PACAP respectively). These data show that cAMP contributes to hypoxic pial artery dilation. Hypoxia increases CSF PACAP while PACAP elevates CSF opioid concentration. These data, therefore, suggest that PACAP modulates cAMP induced opioid release, thereby contributing to hypoxic pial dilation. 

Received 27 June 1996; accepted in final form 17 September 1996.
APS Manuscript Number H575-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 November 1996