Relationship between nitric oxide 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
APStracts 2:0376H, 1995.
Previously, it has been observed that nitric oxide (NO) and the
opioids methionine enkephalin (Met) and leucine enkephalin (Leu)
contribute to hypoxia-induced pial artery dilation in the newborn
pig. The present study was designed to investigate the relationship
between NO and opioids in hypoxic pial dilation. Piglets equipped
with closed cranial windows were used to measure pial artery diameter
and collect cortical periarachnoid CSF for assay of opioids. Sodium
nitroprusside (SNP) (10-8M,10-6M), elicited pial dilation that was
blunted by the soluble guanylate cyclase inhibitor LY 83583 (10-5M)
(10+1 and 23+1 vs 3+1 and 7+1% for 10-8,10-6M SNP before and after LY
83583, respectively). SNP-induced dilation was accompanied by
increased CSF MET and coadministration of LY 83583 with SNP blocked
these increases in CSF opioid concentration (1144+59, 2215+165, and
3413 + 168 vs 1023 +16, 1040+18, and 1059+29 pg/ml for control, 10-8,
10-6M SNP before and after LY 83583 respectively). SNP-induced
release of CSF Leu was also blocked by LY 83583. Similar blunted
vascular and biochemical effects of SNP were observed with
coadministration of the purported cGMP antagonist, Rp 8-Bromo-cGMPs
(10-5M). The cGMP analogue, 8-Bromo-cGMP, elicited dilation that was
also accompanied by increased CSF Met and Leu. Vascular and
biochemical effects of 8-Bromo-cGMP were blunted by Rp 8-Bromo-cGMPs
and unchanged by LY 83583. Hypoxia-induced pial artery dilation was
attenuated by LNA (10-6M), an NO synthase inhibitor (25+2 vs 14+1%).
Hypoxic pial dilation was accompanied by increased CSF Met and these
increases were attenuated by LNA (1137+60 and 3491+133 vs 927+25 and
2052+160 pg/ml for control and hypoxia before and after LNA,
respectively). Hypoxia also increased CSF Leu and these CSF changes
were similarly attenuated by LNA. These data show that cGMP increases
CSF Met and Leu. Further, these data suggest that NO contributes to
hypoxic dilation, at least in part, via formation of cGMP and the
subsequent release of opioids.
Received 17 May 1995; accepted in final form 14 August 1995.
APS Manuscript Number H466-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 15 September 1995.