Superoxide modulates myogenic contractions of mouse afferent arterioles.
Superoxide modulates myogenic contractions of mouse afferent arterioles.
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超氧化物调节小鼠传入动脉的肌源性收缩。
DOI：
10.1161/hypertensionaha.111.170472
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发表时间：
2011-10
期刊：
影响因子：
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通讯作者：
Wilcox CS
中科院分区：
文献类型：
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作者：
Lai EY;Wellstein A;Welch WJ;Wilcox CS
活性氧增强或损害自我调节。由于超氧化物是一种血管收缩剂，我们测试了拉伸产生超氧化物介导肌生成反应的假设。小鼠离体肾传入小动脉灌注压力从40 mmHg升高至80 mmHg，使其直径减小13.3±1.8% (p < 0.001)，使活性氧（乙硫：二氢乙硫荧光）增加9.8±2.3% （p < 0.05）。与天麻酚（3.7±0.8%）、聚乙二醇化超氧化物歧化酶（3.2±1.0%）或罗布麻碱（3.5±0.9%）孵育后拉伸诱导的荧光显著降低（p<0.05），而聚乙二醇化过氧化氢酶、l -硝基精氨酸甲基酯或无Ca2+培养基均无显著降低（p<0.05），这与Ca2+非依赖性血管超氧化物有关。与对照组相比，聚乙二醇化超氧化物歧化酶（5.4±0.8）、天冬氨酸（4.1±1.0%）、罗布麻素（1.0±1.3%）和二苯基碘（3.9±0.9%）显著降低了基底张力和肌原性收缩（p<0.05），而聚乙二醇化过氧化氢酶（10.1±1.6%）没有显著降低。l -硝基精氨酸甲基酯增强了基础张力，但其（15.8±3.3%）和内皮型一氧化氮合酶敲除（10.2±1.8%）均未显著改变肌原性收缩。经超氧化物歧化酶处理后，Tempol无进一步作用，但经过氧化氢酶处理后仍有效。50μM以上的H2O2可引起肌肉收缩，25μM以上的H2O2可抑制肌原性反应（7.4%±0.8%;p< 0.01）。综上所述，传入小动脉内压力的增加导致Ca2+不依赖于烟酰胺腺嘌呤二核苷酸磷酸氧化酶的血管超氧化物的产生增加，这在很大程度上独立于一氧化氮，而H2O2损害压力诱导的收缩，但与正常的肌生成反应无关。
Reactive oxygen species enhance or impair autoregulation. Since superoxide is a vasoconstrictor, we tested the hypothesis that stretch generates superoxide that mediates myogenic responses. Increasing perfusion pressure of mouse isolated perfused renal afferent arterioles from 40 to 80 mmHg reduced their diameter by 13.3 ± 1.8 % (p < 0.001) and increased reactive oxygen species (ethidium: dihydroethidium fluorescence) by 9.8 ± 2.3 % (p < 0.05). Stretch-induced fluorescence was reduced significantly (p<0.05) by incubation with tempol (3.7 ± 0.8%), pegylated superoxide dismutase (3.2 ± 1.0%) or apocynin (3.5 ± 0.9%) but not by pegylated catalase, L-Nitroarginine methylester or Ca2+-free medium, relating it to Ca2+-independent vascular superoxide. Compared to vehicle, basal tone and myogenic contractions were reduced significantly (p<0.05) by pegylated superoxide dismutase (5.4±0.8), tempol (4.1 ± 1.0 %) apocynin (1.0 ± 1.3%;) and diphenyleneiodinium (3.9 ± 0.9%) but not by pegylated catalase (10.1 ± 1.6 %). L-Nitroarginine methylester enhanced basal tone but neither it (15.8 ± 3.3%), nor endolethlial nitric oxide synthase knockout (10.2 ± 1.8%) significantly changed myogenic contractions. Tempol had no further effect after superoxide dismutase but remained effective after catalase. H2O2 above 50μM caused contractions but at 25μM inhibited myogenic responses (7.4 ± 0.8%; p< 0.01). In conclusion, increasing the pressure within afferent arterioles led to Ca2+-independent increased vascular superoxide production from nicotinamide adenine dinucleotide phosephate oxidase which enhanced myogenic contractions largely independent of nitric oxide whereas H2O2 impaired pressure-induced contractions but was not implicated in the normal myogenic response.