The Contribution of δ1- and δ2-Opioid Receptors to Hypoxia-Induced Pial Artery Dilation in the Newborn Pig

Abstract

Previously, it has been observed that mu-opioid receptors contribute to while kappa-opioid receptors oppose pial artery dilation in response to hypoxia. The present study was designed to investigate the contribution of delta 1- and delta 2-opioid receptor activation to hypoxia-induced pial vasodilation. Newborn pigs equipped with a closed cranial window were used to measure pial artery diameter and collect cortical periarachnoid CSF for assay of opioids. Hypoxia increased CSF leucine enkephalin (a delta -agonist) from 36 +/- 6 to 113 +/- 17 pg/ml (n = 5). Hypoxia-induced pial artery vasodilation was attenuated during moderate hypoxia (PaO2 approximately 35 mm Hg), while this response was blunted during severe hypoxia (PaO2 approximately 25 mm Hg), by the delta 1-opioid receptor antagonist 7-benzylidenenaltrexone (BNTX; 10(-8) M) (23 +/- 2 vs. 13 +/- 2 and 34 +/- 6 vs. 10 +/- 3% for moderate and severe hypoxia in the absence and presence of BNTX, respectively; n = 5). In contrast, the delta 2-opioid receptor antagonist naltrindole (10(-9) M) blunted pial vasodilation during moderate hypoxia, but only attenuated the vasodilator response during severe hypoxia (22 +/- 2 vs. 8 +/- 2 and 33 +/- 4 vs. 23 +/- 4% for moderate and severe hypoxia in the absence and presence of naltrindole, respectively; n = 5).(ABSTRACT TRUNCATED AT 250 WORDS)