Cardiovascular Research Group, School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham, NG7 2UH, United Kingdom.
Eur J Pharmacol. 2012 Jan 15;674(2-3):384-90. doi: 10.1016/j.ejphar.2011.11.033. Epub 2011 Nov 29.
Hydrogen peroxide (H(2)O(2)) has been shown to participate in endothelium-derived hyperpolarising factor (EDHF)-mediated mechanisms. Vasorelaxation to the endocannabinoid-like N-oleoylethanolamine (OEA) and anandamide has been shown to be endothelium-dependent. Therefore, the principal aim was to investigate whether H(2)O(2) plays a role in vasorelaxation to endocannabinoids in rat mesenteric arteries. We have also investigated the effects of catalase on endothelium-dependent relaxations and vascular responses to H(2)O(2). First- (G1) and third- (G3) order branches of the superior mesenteric artery from male, Wistar rats were mounted in a wire myograph, contracted with methoxamine, and concentration-response curves to anandamide, OEA carbachol or H(2)O(2), were constructed. The influence of nitric oxide production and H(2)O(2) breakdown on these responses were then investigated using L-NAME (300 μM), and catalase (1000 Uml(-1)) respectively. In G1 mesenteric arteries, vasorelaxations to carbachol and H(2)O(2) were inhibited by L-NAME, but not by catalase. Responses to both anandamide and OEA were also unaffected by catalase. In G3 mesenteric arteries, endothelium-dependent relaxations to carbachol were modestly affected by L-NAME, unaffected by catalase alone, but their combination greatly inhibited vasorelaxation. Similarly, catalase inhibited vasorelaxation to anandamide and OEA, and combined treatment with L-NAME further reduced this response. In G1 mesenteric arteries, vasorelaxation to H(2)O(2) is predominantly mediated by nitric oxide. We conclude that in G3 arteries H(2)O(2) activity contributes towards EDHF-type responses and vasorelaxation to endocannabinoids, either directly or indirectly. Given the association between vascular pathophysiology and H(2)O(2), these findings may provide a mechanism whereby disease states may influence responses to endocannabinoid and related mediators.
过氧化氢（H(2)O(2)）已被证明参与内皮衍生超极化因子（EDHF）介导的机制。已经表明，对类大麻素内源性大麻素样 N-油酰乙醇胺（OEA）和大麻素的血管舒张作用是内皮依赖性的。因此，主要目的是研究 H(2)O(2)是否在大鼠肠系膜动脉中对内源性大麻素的血管舒张作用中发挥作用。我们还研究了过氧化氢酶对内皮依赖性舒张作用和血管对 H(2)O(2)的反应的影响。雄性 Wistar 大鼠肠系膜上动脉的第一（G1）和第三（G3）级分支被安装在一个金属丝肌动描记器中，用甲氧胺收缩，并构建了对大麻素、OEA 卡巴胆碱或 H(2)O(2)的浓度反应曲线。然后，使用 L-NAME（300 μM）和过氧化氢酶（1000 Uml(-1)）分别研究了一氧化氮产生和 H(2)O(2)分解对这些反应的影响。在 G1 肠系膜动脉中，L-NAME 抑制了卡巴胆碱和 H(2)O(2)引起的血管舒张，但不抑制过氧化氢酶。OEA 和大麻素的反应也不受过氧化氢酶的影响。在 G3 肠系膜动脉中，内皮依赖性的卡巴胆碱舒张作用受到 L-NAME 的轻微影响，单独使用过氧化氢酶不受影响，但它们的组合大大抑制了血管舒张。同样，过氧化氢酶抑制了大麻素和 OEA 的血管舒张作用，L-NAME 的联合处理进一步降低了这种反应。在 G1 肠系膜动脉中，H(2)O(2)引起的血管舒张主要是通过一氧化氮介导的。我们的结论是，在 G3 动脉中，H(2)O(2)的活性有助于 EDHF 型反应和内源性大麻素的血管舒张，无论是直接还是间接的。鉴于血管病理生理学与 H(2)O(2)之间的关联，这些发现可能提供了一种机制，即疾病状态可能影响内源性大麻素和相关介质的反应。
