Rey Federico E, Li Xiao-Chun, Carretero Oscar A, Garvin Jeffrey L, Pagano Patrick J
Hypertension & Vascular Research Division, Henry Ford Hospital, Detroit, Mich 48202-2689, USA.
Circulation. 2002 Nov 5;106(19):2497-502. doi: 10.1161/01.cir.0000038108.71560.70.
Like endothelial and smooth muscle cells, vascular adventitial fibroblasts contain a substantial NAD(P)H oxidase superoxide anion (O2-)-generating system activated by angiotensin II (Ang II). Based on the ability of nitric oxide (NO*) to diffuse rapidly through tissue and the fast reaction rate of NO* and O2-, we postulated that the interaction between NO. and adventitial NAD(P)H oxidase-derived O2- contributes to impairment of endothelium-dependent relaxation (EDR).
C57Bl/6 mouse abdominal aortas were simultaneously perfused intraluminally and suffused adventitially with physiological buffer at 37 degrees C. After constricting the vessels with phenylephrine, an acetylcholine dose-response curve was obtained while monitoring changes in diameter by videomicroscopy. Endogenous O2- was increased by treating the adventitial side of the aortas with Ang II (10 pmol/L), leading to impairment of EDR. EDR impairment was reversed by adventitial suffusion of superoxide dismutase (SOD) of aortas from wild-type mice. Ang II-treated aortas from gp91(phox-/-) mice, which lack significant adventitial O2-, exhibited greater EDR and were not affected by SOD. Adventitially suffused SOD failed to penetrate the media, indicating that the effects of SOD were localized to the adventitia. Adventitial application of the O2--generating system xanthine/xanthine oxidase or the potent NO scavenger oxyhemoglobin impaired EDR.
O2- derived from adventitial gp91(phox)-based NAD(P)H oxidase contributes to impairment of the action of endothelium-derived NO.
与内皮细胞和平滑肌细胞一样，血管外膜成纤维细胞含有由血管紧张素II（Ang II）激活的大量烟酰胺腺嘌呤二核苷酸磷酸（NAD(P)H）氧化酶超氧阴离子（O2-）生成系统。基于一氧化氮（NO*）能够快速扩散通过组织以及NO与O2-的快速反应速率，我们推测NO与外膜NAD(P)H氧化酶衍生的O2-之间的相互作用导致内皮依赖性舒张（EDR）受损。
将C57Bl/6小鼠腹主动脉在37℃下同时进行腔内灌注和外膜灌注生理缓冲液。用去氧肾上腺素收缩血管后，通过视频显微镜监测直径变化，同时获得乙酰胆碱剂量反应曲线。用Ang II（10 pmol/L）处理主动脉外膜侧可增加内源性O2-，导致EDR受损。野生型小鼠主动脉外膜灌注超氧化物歧化酶（SOD）可逆转EDR受损。来自gp91(phox-/-)小鼠的Ang II处理的主动脉缺乏显著的外膜O2-，表现出更大的EDR，且不受SOD影响。外膜灌注的SOD未能穿透中膜，表明SOD的作用局限于外膜。外膜应用O2-生成系统黄嘌呤/黄嘌呤氧化酶或强效NO清除剂氧合血红蛋白会损害EDR。
源自外膜基于gp91(phox)的NAD(P)H氧化酶的O2-导致内皮衍生的NO作用受损。
