Xanthine oxidase-derived reactive oxygen species convert flow-induced arteriolar dilation to constriction in hyperhomocysteinemia - Possible role of peroxynitrite
Xanthine oxidase-derived reactive oxygen species convert flow-induced arteriolar dilation to constriction in hyperhomocysteinemia - Possible role of peroxynitrite
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DOI：
10.1161/hq0102.101127
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发表时间：
2002-01-01
影响因子：
8.7
通讯作者：
Koller, A
中科院分区：
文献类型：
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作者：
Bagi, Z;Ungvari, Z;Koller, A
我们假设，在高同型半胱氨酸血症（HHcy），流量引起的小动脉收缩是由于活性氧和/或氮的产生增强，导致一氧化氮（NO）和前列腺素介导的反应受损。通过视频显微镜测量来自对照组和蛋氨酸饮食诱导的HHcy大鼠的分离的加压（在80 mm Hg下）股薄肌小动脉（直径约为170 μ m）的直径变化。管腔内流量增加（从0到25穆尔/min）导致NO和肾上腺素介导的对照小动脉扩张（最大值，对照，30+/-4 μ m），但引起HHcy小动脉显著收缩（最大值，HHcy，-32+/-3 μ m），这被血栓烷A（2）受体阻断剂SQ 29，548消除。超氧化物歧化酶加过氧化氢酶的管腔内给药并不影响控制小动脉的流量介导的扩张，但在高同型半胱氨酸小动脉，它扭转了流量引起的收缩扩张（最大18+/-4妈妈），这是废除了NO合酶抑制剂。黄嘌呤氧化酶抑制剂oxypurinol [但NAD（P）H-氧化酶抑制剂diphenyleniodonium]和已知的过氧亚硝酸盐清除剂尿酸盐可阻止血流诱导的HHcy小动脉收缩。此外，真正的过氧亚硝酸盐引起小动脉收缩（-31+/-8 μ m），尿酸盐和SQ 29，548消除了这种收缩。因此，我们认为，在高同型半胱氨酸，黄嘌呤氧化酶衍生的超氧化物清除NO释放到流动，形成过氧亚硝酸盐，促进血栓素A（2）的释放，导致小动脉收缩。
We hypothesized that in hyperhomocysteinemia (HHcy), flow-induced arteriolar constriction is due to an enhanced generation of reactive oxygen and/or nitrogen species, causing an impairment of nitric oxide (NO) and prostaglandin mediation of the response. Changes in diameter of isolated, pressurized (at 80 mm Hg) gracilis muscle arterioles (diameter approximate to 170 mum) from control and methionine diet-induced HHcy rats were measured by videomicroscopy. Increases in intraluminal flow (from 0 to 25 muL/min) resulted in NO- and prostaglandin-mediated dilations of control arterioles (maximum, control, 30+/-4 mum) but elicited significant constrictions of HHcy arterioles (maximum, HHcy, -32+/-3 mum), which were abolished by the thromboxane A(2) receptor blocker SQ 29,548. Intraluminal administration of superoxide dismutase plus catalase did not affect flow-mediated dilations of control arterioles, but in HHcy arterioles, it reversed the flow-induced constrictions to dilations (maximum 18+/-4 mum), which were abolished by an NO synthase inhibitor. Flow-induced constrictions of HHcy arterioles were prevented by the presence of the xanthine oxidase inhibitor oxypurinol [but not by the NAD(P)H-oxidase inhibitor diphenyleneiodonium] and by urate, a known peroxynitrite scavenger. Also, authentic peroxynitrite elicited arteriolar constrictions (-31+/-8 mum) that were eliminated by urate and SQ 29,548. Thus, we suggest that in HHcy, xanthine oxidase-derived superoxide scavenges NO released to flow, forming peroxynitrite, which promotes release of thromboxane A(2), resulting in arteriolar constriction.