Armstead W M
Department of Anesthesia, University of Pennsylvania, Philadelphia, USA.
J Cereb Blood Flow Metab. 1995 May;15(3):539-46. doi: 10.1038/jcbfm.1995.67.
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)
此前已有研究观察到，μ-阿片受体可促使软脑膜动脉扩张，而κ-阿片受体则会抑制缺氧引起的软脑膜动脉扩张。本研究旨在探究δ1-和δ2-阿片受体激活对缺氧诱导的软脑膜血管舒张的作用。使用配备封闭颅窗的新生猪来测量软脑膜动脉直径，并收集皮质蛛网膜下腔脑脊液以检测阿片类物质。缺氧使脑脊液亮氨酸脑啡肽（一种δ-激动剂）从36±6 pg/ml增加至113±17 pg/ml（n = 5）。在中度缺氧（动脉血氧分压约35 mmHg）期间，缺氧诱导的软脑膜动脉血管舒张减弱，而在重度缺氧（动脉血氧分压约25 mmHg）期间，δ1-阿片受体拮抗剂7-亚苄基纳曲酮（BNTX；10⁻⁸ M）使这种反应减弱（在不存在和存在BNTX的情况下，中度缺氧时分别为23±2%和13±2%，重度缺氧时分别为34±6%和10±3%；n = 5）。相比之下，δ2-阿片受体拮抗剂纳曲吲哚（10⁻⁹ M）在中度缺氧时减弱软脑膜血管舒张，但仅在重度缺氧时减弱血管舒张反应（在不存在和存在纳曲吲哚的情况下，中度缺氧时分别为22±2%和8±2%，重度缺氧时分别为33±4%和23±4%；n = 5）。（摘要截断于250字）
