Frisbee J C, Roman R J, Krishna U M, Falck J R, Lombard J H
Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisc 53226, USA.
J Vasc Res. 2001 Jul-Aug;38(4):305-14. doi: 10.1159/000051061.
This study determined the contribution of prostanoids, cytochrome P450 (CP450) 4A enzyme metabolites of arachidonic acid, and other potential mediators of hypoxic dilation of isolated rat skeletal muscle resistance arteries. Gracilis arteries (GA) were viewed via television microscopy and dilator responses to hypoxia (reduction in superfusate and perfusate PO2 from approximately 145 to approximately 40 mm Hg) were measured with a video micrometer. Hypoxic dilation of gracilis arteries was severely impaired by either endothelium removal or cyclooxygenase inhibition with indomethacin, but not by nitric oxide synthase inhibition with L-NAME. Treatment of GA with 17-octadecynoic acid (17-ODYA) alone to inhibit CP450 4A enzymes significantly reduced hypoxic dilation from control levels. Treatment of vessels with N-methylsulfonyl-6-(2-proparglyoxyphenyl)hexanoic acid (MS-PPOH) to inhibit the production of epoxyeicosatrienoic acids (EETs) did not alter hypoxic dilation, although treatment with dibromo-dodecenyl-methylsulfimide (DDMS) to inhibit 20-hydroxyeicosatetraenoic acid (20-HETE) production had similar effects as 17-ODYA. Treatment of GA with 6(Z),15(Z)-20-HEDE, a competitive antagonist of the actions of 20-HETE, mimicked the effects of 17-ODYA and DDMS treatment on hypoxic dilation. These results suggest that hypoxic dilation of skeletal muscle resistance arteries primarily represents the effects of enhanced prostanoid release from vascular endothelium, although a contribution of reduced 20-HETE production via CP450 omega-hydroxylase enzymes also regulates hypoxic dilation of these vessels.
本研究确定了类前列腺素、花生四烯酸的细胞色素P450（CP450）4A酶代谢产物以及其他参与离体大鼠骨骼肌阻力动脉缺氧性舒张的潜在介质所起的作用。通过电视显微镜观察股薄肌动脉（GA），并用视频测微计测量其对缺氧（将 superfusate 和灌注液的 PO₂ 从约 145 mmHg 降至约 40 mmHg）的舒张反应。去除内皮或用吲哚美辛抑制环氧化酶均可严重损害股薄肌动脉的缺氧性舒张，但用 L-NAME 抑制一氧化氮合酶则无此作用。单独用 17-十八炔酸（17-ODYA）处理 GA 以抑制 CP450 4A 酶，可使缺氧性舒张从对照水平显著降低。用 N-甲基磺酰基-6-(2-炔丙氧基苯基)己酸（MS-PPOH）处理血管以抑制环氧二十碳三烯酸（EETs）的生成，并未改变缺氧性舒张，尽管用二溴-十二碳烯基-甲基磺酰亚胺（DDMS）处理以抑制 20-羟基二十碳四烯酸（20-HETE）的生成与 17-ODYA 有相似作用。用 6(Z),15(Z)-20-HEDE（一种 20-HETE 作用的竞争性拮抗剂）处理 GA，可模拟 17-ODYA 和 DDMS 处理对缺氧性舒张的影响。这些结果表明，骨骼肌阻力动脉的缺氧性舒张主要表现为血管内皮释放类前列腺素增加的作用，尽管通过 CP450 ω-羟化酶减少 20-HETE 的生成也参与调节这些血管的缺氧性舒张。
