Apocynin normalizes hyperreactivity to phenylephrine in mesenteric arteries from cholesterol-fed mice by improving endothelium-derived hyperpolarizing factor response
Apocynin normalizes hyperreactivity to phenylephrine in mesenteric arteries from cholesterol-fed mice by improving endothelium-derived hyperpolarizing factor response
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DOI：
10.1016/j.freeradbiomed.2006.07.012
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发表时间：
2006-10-15
影响因子：
7.4
通讯作者：
Kamata, Katsuo
中科院分区：
文献类型：
--
作者：
Matsumoto, Takayuki;Miyamori, Kiyoto;Kamata, Katsuo
我们研究了内皮功能、氧化应激和去氧肾上腺素（PE；α(1)-肾上腺素受体激动剂）诱导的高胆固醇（HQ 饮食喂养小鼠）肠系膜动脉收缩之间的关系。在 HC 小鼠（与年龄匹配的正常饮食喂养小鼠）中：（1）PE 诱导的完整内皮环收缩增强（内皮剥脱增加“正常饮食”环，但在“HC”环中没有进一步增强）；（2）在 N-G-硝基-L-精氨酸（L-NNA；一氧化氮合酶抑制剂）或 L-NNA 加吲哚美辛（环氧合酶抑制剂）[以保留内皮源性超极化因子（EDHF）]的存在下，增强的 PE 诱导的收缩进一步增强，但在 Charybdotoxin 加 apamin 的存在下没有变化（以阻断） (3) ACh 诱导的 EDHF 型松弛减少；(4) HC 小鼠的氧化应激[由血浆 8-异前列腺素水平（可靠的全身标记物）和主动脉超氧化物产生表示]更大，夹竹桃麻素 [NAD(P)H 氧化酶抑制剂] 或 tempol（超氧化物歧化酶模拟物）使 PE 诱导的收缩正常化，但由 NADH [NAD(P)H] 增强。口服膳食补充罗布麻素（30 mg/kg/天，持续 4 周）可纠正上述异常情况。因此：(1) PE 诱导的收缩是由内皮细胞调节的，HC 小鼠的收缩力增强是由于 EDHF 信号传导缺陷和氧化应激升高所致，(2) 罗布麻素通过改善 EDHF 信号传导使 PE 诱导的收缩正常化 (c) 2006 Elsevier Inc. 保留所有权利。
We studied the relationship among endothelial function, oxidative stress, and phenylephrine (PE; alpha(1)-adrenoceptor agonist)-induced contraction in mesenteric arteries from high-cholesterol (HQ-diet-fed mice. In HC mice (vs age-matched normal-diet-fed mice): (1) PE-induced contraction in endothelium-intact rings was enhanced (endothelial denudation increased contraction in "normal-diet" rings, but did not enhance it further in "HC" rings); (2) the enhanced PE-induced contraction was further enhanced in the presence of N-G-nitro-L-arginine (L-NNA; nitric oxide synthase inhibitor) or L-NNA plus indomethacin (cyclooxygenase inhibitor) [to preserve endothelium-derived hyperpolarizing factor (EDHF)], but unchanged in the presence of charybdotoxin plus apamin (to block EDHF); (3) ACh-induced EDHF-type relaxation was reduced; and (4) oxidative stress [indicated by the plasma 8-isoprostane level (reliable systemic marker) and aortic superoxide production] was greater. In HC mice, PE-induced contraction was normalized by apocynin [NAD(P)H oxidase inhibitor] or tempol (superoxide dismutase mimetic), but enhanced by NADH [NAD(P)H oxidase substrate]. Oral dietary supplementation with apocynin (30 mg/kg/day for 4 weeks) corrected the above abnormalities. Hence: (1) PE-induced contraction is modulated by the endothelium, and the enhanced contractility in HC mice results from defective EDHF signaling and elevated oxidative stress, and (2) apocynin normalizes PE-induced contraction in HC mice by improving EDHF signaling. (c) 2006 Elsevier Inc. All rights reserved.