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缺氧对被脂肪组织包围的小鼠肠系膜动脉的影响。

Effect of hypoxia in mice mesenteric arteries surrounded by adipose tissue.

机构信息

Department of Pharmacology, Ghent University, De Pintelaan, Belgium.

出版信息

Acta Physiol (Oxf). 2011 Sep;203(1):235-44. doi: 10.1111/j.1748-1716.2010.02238.x. Epub 2011 Mar 1.

Abstract

AIM

To investigate the influence of hypoxia on the vasoactive effect of peri-vascular white adipose tissue.

METHODS

Isometric tension recordings were performed on mesenteric arteries from Swiss male mice with or without adherent adipose tissue.

RESULTS

Hypoxia (bubbling with 95% N(2), 5% CO(2)) induced a biphasic response, i.e. vasoconstriction followed by vasorelaxation, in pre-contracted (noradrenaline, 10 μm) mesenteric arteries with adipose tissue in the presence of indomethacin (10 μm) and N(ω) -nitro-l-arginine (0.1 mm). Only a small vasorelaxation was observed in arteries without adipose tissue. Pre-contraction with 60 or 120 mm K(+) , incubation with tetraethylammoniumchloride (1 and 3 mm), apamin (1 μm) combined with charybdotoxin (0.1 μm) or 1-[(2-chlorophenyl) diphenylmethyl]-1H-pyrazole (TRAM-34) (10 μm) significantly impaired the hypoxic vasorelaxation. Removal of the endothelium only reduced the hypoxic vasorelaxation. Apamin (1 μm) and charybdotoxin (0.1 μm) did not influence the vasorelaxation of sodium hydrosulfide hydrate. Zinc protoporphyrin IX (10 μm), miconazole (10 μm), 8-(p-sulfophenyl)theophylline (0.1 mm), 1 H-[1, 2, 4]oxadiazolo[4,3- A]quinoxalin-1-one (10 μm), apocynin (0.3 mm), diphenyliodonium (1 μm), catalase (2500 U mL(-1)) and tempol (0.1 mm) did not influence the hypoxic vasorelaxation. In contrast to losartan (0.1 mm), indomethacin (10 μm) and SQ-29548 (10 μm) significantly reduced the hypoxic vasoconstriction.

CONCLUSIONS

Moderate hypoxia induces a biphasic vasomotor response in mice mesenteric arteries surrounded by adipose tissue. The hypoxic vasoconstriction is endothelium independent, whereas the vasodilation is endothelium dependent, soluble guanylyl cyclase independent and in part mediated by opening K(Ca) channels. Cyclooxygenase metabolites mediate the hypoxic vasoconstriction, while endothelium-derived hyperpolarizing factor plays a small role in the hypoxic vasorelaxation.

摘要

目的

探讨低氧对血管周白色脂肪组织血管活性的影响。

方法

在有或没有附着脂肪组织的瑞士雄性小鼠肠系膜动脉上进行等长张力记录。

结果

低氧(用 95% N(2)、5% CO(2) 鼓泡)在存在吲哚美辛(10μm)和 N(ω)-硝基-L-精氨酸(0.1mm)的情况下,在预先收缩(去甲肾上腺素,10μm)的肠系膜动脉中引起双相反应,即血管收缩后血管舒张,而在没有脂肪组织的动脉中仅观察到较小的血管舒张。用 60 或 120mm K(+)预收缩,用四乙铵氯(1 和 3mm)、阿帕米(1μm)联合巴拉胺(0.1μm)或 1-[(2-氯苯基)二苯基甲基]-1H-吡唑(TRAM-34)(10μm)孵育显著损害了低氧诱导的血管舒张。去除内皮仅减少了低氧诱导的血管舒张。阿帕米(1μm)和巴拉胺(0.1μm)不影响水合亚硫酸氢钠的血管舒张。锌原卟啉 IX(10μm)、咪康唑(10μm)、8-(对磺苯基)茶碱(0.1mm)、1H-[1,2,4]恶二唑[4,3-A]喹喔啉-1-酮(10μm)、阿朴肉桂醇(0.3mm)、二苯碘翁(1μm)、过氧化氢酶(2500UmL(-1))和特布他林(0.1mm)不影响低氧诱导的血管舒张。与氯沙坦(0.1mm)相比,吲哚美辛(10μm)和 SQ-29548(10μm)显著降低了低氧引起的血管收缩。

结论

中度低氧诱导小鼠肠系膜动脉周围脂肪组织的双相血管运动反应。低氧引起的血管收缩是内皮非依赖性的,而血管舒张是内皮依赖性的,可溶性鸟苷酸环化酶非依赖性的,部分是通过开放 K(Ca)通道介导的。环氧化酶代谢物介导低氧引起的血管收缩,而内皮源性超极化因子在低氧引起的血管舒张中作用较小。

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