Virdis Agostino, Neves Mario Fritsch, Amiri Farhad, Touyz Rhian M, Schiffrin Ernesto L
CIHR Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montreal, University of Montreal, Quebec, Canada.
J Hypertens. 2004 Mar;22(3):535-42. doi: 10.1097/00004872-200403000-00016.
Angiotensin (Ang) II stimulates vascular reactive oxygen species generation via NAD(P)H oxidase activation. We investigated whether vascular NAD(P)H oxidase influences structure and function of resistance arteries from Ang II-infused mice.
Mice received Ang II alone (400 ng/kg per min, subcutaneously), Ang II + apocynin (NAD(P)H oxidase inhibitor, 2.5 mg/day, in the food), apocynin alone or Ang II + hydralazine (50 mg/kg per day) for 14 days. Systolic blood pressure (SBP) was measured by tail-cuff methodology and function and structure of small mesenteric arteries were studied in pressurized vessels. Vascular collagen type I/III content was evaluated by confocal immunofluorescence microscopy and by immunoblotting.
The rise in SBP induced by Ang II (P < 0.001) was prevented by apocynin and hydralazine. Media/lumen ratio increase in Ang II-infused mice (P < 0.01) was prevented by apocynin. Acetylcholine-mediated relaxation, which was impaired in Ang II-infused mice (P < 0.001), was improved by apocynin. Confocal microscopy and immunoblotting demonstrated increased collagen type I/III content in mesenteric arteries from Ang II-infused mice. Apocynin, but not hydralazine, prevented the increase in collagen abundance in Ang II-infused mice. The increase in vascular NAD(P)H oxidase activity by Ang II (P < 0.001) was prevented by apocynin.
The NAD(P)H oxidase inhibitor apocynin reduced blood pressure elevation and prevented structural alterations, endothelial dysfunction, and collagen deposition in the media of small arteries in Ang II-infused mice. Although hydralazine also decreased blood pressure, it had no effects on vascular collagen content. Our findings suggest that NAD(P)H oxidase activity plays an important role in vascular functional and structural changes and in the composition of the vascular wall in Ang II-dependent hypertension.
血管紧张素（Ang）II 通过激活 NAD(P)H 氧化酶刺激血管活性氧生成。我们研究了血管 NAD(P)H 氧化酶是否影响 Ang II 灌注小鼠阻力动脉的结构和功能。
小鼠分别接受单独的 Ang II（400 ng/kg 每分钟，皮下注射）、Ang II + 阿朴吗啡（NAD(P)H 氧化酶抑制剂，2.5 mg/天，加入食物中）、单独的阿朴吗啡或 Ang II + 肼屈嗪（50 mg/kg 每天），持续 14 天。采用尾套法测量收缩压（SBP），并在压力血管中研究小肠系膜小动脉的功能和结构。通过共聚焦免疫荧光显微镜和免疫印迹评估血管 I 型/III 型胶原蛋白含量。
阿朴吗啡和肼屈嗪可预防 Ang II 诱导的 SBP 升高（P < 0.001）。阿朴吗啡可预防 Ang II 灌注小鼠的中膜/管腔比值增加（P < 0.01）。阿朴吗啡可改善 Ang II 灌注小鼠受损的乙酰胆碱介导的舒张功能（P < 0.001）。共聚焦显微镜和免疫印迹显示，Ang II 灌注小鼠肠系膜动脉中 I 型/III 型胶原蛋白含量增加。阿朴吗啡而非肼屈嗪可预防 Ang II 灌注小鼠胶原蛋白丰度的增加。阿朴吗啡可预防 Ang II 诱导的血管 NAD(P)H 氧化酶活性增加（P < 0.001）。
NAD(P)H 氧化酶抑制剂阿朴吗啡可降低 Ang II 灌注小鼠的血压升高，并预防小动脉中膜的结构改变、内皮功能障碍和胶原蛋白沉积。虽然肼屈嗪也可降低血压，但对血管胶原蛋白含量无影响。我们的研究结果表明，NAD(P)H 氧化酶活性在 Ang II 依赖性高血压的血管功能和结构变化以及血管壁组成中起重要作用。
