Hatoum Ossama A, Binion David G, Miura Hiroto, Telford Gordon, Otterson Mary F, Gutterman David D
Cardiovascular Research Center, Department of Surgery, Froedtert Memorial Lutheran Hospital, Veterans Affairs Medical Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Am J Physiol Heart Circ Physiol. 2005 Jan;288(1):H48-54. doi: 10.1152/ajpheart.00663.2004. Epub 2004 Sep 2.
The endothelium plays an important role in maintaining vascular homeostasis by synthesizing and releasing several mediators of vasodilation, which include prostacyclin (PGI(2)), nitric oxide, and endothelium-derived hyperpolarizing factor (EDHF). We have recently defined the role of nitric oxide and PGI(2) in the dilation of submucosal intestinal arterioles from patients with normal bowel function. However, significant endothelium-dependent dilator capacity to ACh remained after inhibiting both these mediators. The current study was designed to examine the potential role of EDHF in human intestinal submucosal arterioles. ACh elicited endothelium-dependent relaxation in the presence of inhibitors of nitric oxide synthase and cyclooxygenase (23 +/- 10%, n = 6). This ACh-induced relaxation was inhibited and converted to constriction by catalase (-53 +/- 10%, n = 6) or KCl (-30 +/- 3%, n = 7), whereas 17-octadecynoic acid and 6-(2-propargylloxyphenyl) hexanoic acid, two inhibitors of cytochrome P450 monooxygenase, had no significant effect (3 +/- 1% and 20 +/- 8%, n = 5, respectively). Exogenous H(2)O(2) elicited dose-dependent relaxation of intact microvessels (52 +/- 10%, n = 7) but caused frank vasoconstriction in arterioles denuded of endothelium (-73 +/- 8%, n = 7). ACh markedly increased the dichlorofluorescein fluorescence in intact arterioles in the presence of nitric oxide synthase and cyclooxygenase inhibitors compared with control and compared with catalase-treated microvessels (363.6 +/- 49, 218.8 +/- 10.6, 221.9 +/- 27.9, respectively, P < 0.05 ANOVA, n = 5 arbitrary units). No changes in the dichlorofluorescein fluorescence were recorded in vessels treated with ACh alone. These results indicate that endothelial production of H(2)O(2) occurs in response to ACh in human gut mucosal arterioles but that H(2)O(2) is not an EDHF in this tissue. Rather, we speculate that it stimulates the release of a chemically distinct EDHF.
内皮细胞通过合成和释放多种血管舒张介质，在维持血管稳态中发挥重要作用，这些介质包括前列环素（PGI₂）、一氧化氮和内皮衍生超极化因子（EDHF）。我们最近确定了一氧化氮和PGI₂在肠功能正常患者的黏膜下肠小动脉舒张中的作用。然而，在抑制这两种介质后，乙酰胆碱（ACh）引起的显著内皮依赖性舒张能力仍然存在。本研究旨在探讨EDHF在人肠黏膜下小动脉中的潜在作用。在一氧化氮合酶和环氧化酶抑制剂存在的情况下，ACh引起内皮依赖性舒张（23±10%，n = 6）。这种ACh诱导的舒张被过氧化氢酶抑制并转变为收缩（-53±10%，n = 6）或氯化钾（-30±3%，n = 7），而细胞色素P450单加氧酶的两种抑制剂17-十八炔酸和6-（2-炔丙氧基苯基）己酸没有显著作用（分别为3±1%和20±8%，n = 5）。外源性过氧化氢引起完整微血管的剂量依赖性舒张（52±10%，n = 7），但在去除内皮的小动脉中引起明显的血管收缩（-73±8%，n = 7）。与对照相比，在一氧化氮合酶和环氧化酶抑制剂存在的情况下，ACh显著增加了完整小动脉中的二氯荧光素荧光，与过氧化氢酶处理的微血管相比也是如此（分别为363.6±49、218.8±10.6、221.9±27.9，P < 0.05，方差分析，n = 5个任意单位）。单独用ACh处理的血管中未记录到二氯荧光素荧光的变化。这些结果表明，人肠黏膜小动脉中内皮细胞会响应ACh产生过氧化氢，但过氧化氢在该组织中不是EDHF。相反，我们推测它会刺激化学性质不同的EDHF的释放。
