THE CONTRIBUTION OF DELTA(1)-OPIOID AND DELTA(2)-OPIOID RECEPTORS TO HYPOXIA-INDUCED PIAL ARTERY DILATION IN THE NEWBORN PIG

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 approximate to 35 mm Hg), while this response was blunted during severe hypoxia (PaO2 approximate to 25 mm Hg), by the delta(1)-opioid receptor antagonist 7-benzylidenen-altrexone (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). Receptor selectivity experiments show that BNTX blocked responses to the delta(1)-agonist DPDPE, whereas responses to the delta(2)-agonist deltorphin II were unchanged (12 +/- 3 vs. 2 +/- 1% and 14 +/- 4 vs. 14 +/- 3% for DPDPE at 10(-6) M and deltorphin II at 10(-6) M in the absence and presence of BNTX; n = 5). Similarly, naltrindole blocked responses to deltorphin II, but responses to DPDPE were unchanged. These data indicate that delta(1)-receptor activation contributes to both moderate and severe hypoxia-induced vasodilation, but the delta(1)-receptors appear to be more important during severe hypoxia relative to delta(2)-receptors. Additionally, these data show that delta(2)-receptors primarily contribute to dilation during moderate hypoxia.