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)