11,12-环氧二碳三烯酸在大鼠灌注肠系膜血管中诱导血管扩张反应

S. M. Bihzad, M. H. M. Yousif
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引用次数: 2

摘要

环氧二碳三烯酸(EETs)是一种内源性配体,可被可溶性环氧化物水解酶(sEH)水解。研究了11,12 - eet与其他血管扩张激动剂(包括萘酚和硝普钠)的反应。研究1-环己基-3-十二烷基脲(CDU, sEH)对11,12 - eet对正常血糖和1型stz糖尿病大鼠肠系膜床血管舒张作用的影响。在对照组和糖尿病动物的肠系膜灌注床中,11,12 - eet以剂量依赖的方式产生血管舒张。11,12 - eet诱导的血管扩张反应在糖尿病动物的组织中显著降低,但通过抑制sEH显著纠正了这一点。研究了一氧化氮合酶抑制剂、环氧合酶抑制剂、特异性钾通道抑制剂、可溶性胍基环化酶抑制剂和瞬时受体电位通道V4抑制剂对11,12 - eet血管舒张剂反应的影响。在从对照动物分离的组织中,l-NAME、l-NAME与吲哚美辛、格列本脲、iberiotoxin、charybdotoxin、apamin或ODQ急性孵育均未抑制血管扩张剂对11,12 - eet的反应。与瞬时受体电位通道V4抑制剂钌红孵育可显著降低11,12 - eet诱导的血管舒张反应。综上所述,本研究结果表明11,12 - eet在灌注的肠系膜床中具有血管扩张作用,部分是通过激活香草素受体来实现的。提高EETs水平的策略可能对纠正糖尿病相关微血管异常有重要影响。
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11,12-Epoxyeicosatrienoic acid induces vasodilator response in the rat perfused mesenteric vasculature

  1. Epoxyeicosatrienoic acids (EETs) are endogenous ligands that undergo hydrolysis by soluble epoxide hydrolase (sEH). The responses of 11, 12-EET in comparison with other vasodilator agonists including carbachol and sodium nitroprusside (SNP) were investigated. The effect of 1-cyclohexyl-3-dodecyl urea (CDU), a sEH, was tested on the vasodilator effect induced by 11, 12-EET in the perfused mesenteric beds isolated from normo-glycaemic and type-1 STZ-diabetic rats.
  2. In the perfused mesenteric beds of control and diabetic animals, 11, 12-EET produced vasodilation in a dose-dependent manner. The vasodilator response induced by 11, 12-EET was significantly decreased in tissues obtained from diabetic animals, but this was significantly corrected through inhibition of sEH.
  3. The effects of nitric oxide synthase inhibitor, cyclo-oxygenase inhibitor, specific potassium channel inhibitors, soluble guanylyl cyclase inhibitor and transient receptor potential channel V4 inhibitor, on vasodilator response to 11, 12-EET were investigated.
  4. In tissues isolated from control animals, vasodilator responses to 11, 12-EET were not inhibited by acute incubation with l-NAME, l-NAME with indomethacin, glibenclamide, iberiotoxin, charybdotoxin, apamin or ODQ.
  5. Incubation with the transient receptor potential channel V4 inhibitor ruthenium red caused significantly reduced vasodilator responses induced by 11, 12-EET.
  6. In conclusion, results from this study indicate that 11, 12-EET has a vasodilator effect in the perfused mesenteric bed, partly through activation of vanilloid receptor. A strategy to elevate the levels of EETs may have a significant impact in correcting microvascular abnormality associated with diabetes.
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Issue Information Autonomic and Autacoid Pharmacology: Goodbye and thank you Attenuation of the anti-contractile effect of cooling in the rat aorta by perivascular adipose tissue Retraction: Dopamine receptor immunohistochemistry in the rat choroid plexus. Issue Information
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