Aging-related induction of inducible nitric oxide synthase is vasculo-protective to the arterial media

Aging-related induction of inducible nitric oxide synthase is vasculo-protective to the arterial media
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DOI:
10.1016/j.cardiores.2003.12.006
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发表时间:
2004-03-01
影响因子:
10.8
通讯作者:
Rajfer, J
Rajfer, J
中科院分区:
医学1区
文献类型:
--
作者:
Ferrini, MG;Davila, HH;Rajfer, J

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目的:衰老相关的勃起功能障碍(ED)主要是由平滑肌细胞(SMC)减少和海绵体内胶原蛋白增加引起的,推测这是由于活性氧(ROS)增加所致。伴随着诱导型一氧化氮合酶 (NOS) 的表达,产生一氧化氮,清除 ROS 并抑制胶原蛋白沉积。我们研究了随着年龄的增长,动脉中膜 SMC 内是否会发生类似的过程,这些过程与海绵体 SMC 具有一些共同的生理功能。方法:老年(22-24 个月)雄性棕色挪威大鼠接受含有或不含 NOS 活性抑制剂(L-N-(亚氨基乙基)-赖氨酸乙酸盐 [L-NEL],0.1 g/l)的水,持续 3 周。未治疗的年轻(3个月)大鼠用作对照(每组n=5)。对阴茎、腹主动脉、股动脉和肱动脉的组织切片进行胶原蛋白、SMC、NOS、ROS 纤溶酶原激活剂抑制剂 (PAI) 和细胞凋亡的染色,并通过定量图像分析进行评估。还通过 GSH/GSSG 比率测定新鲜组织和全血中的 ROS。结果:据观察,从主动脉到阴茎阻力动脉的动脉树中层中大多数由衰老引起的变化与海绵体中发生的变化相似,即 SMC/胶原比率降低以及 ROS 和 NOS 增加,特别是在阻力动脉的情况下,SMC 凋亡增加和 L-NIL 抑制 PAL NOS 进一步增加 ROS 并降低 SMC/胶原比率。媒体。结论:这些观察结果表明,老年男性的 ED 和动脉硬化可能具有共同的病因,并且 SMC 表达 NOS 是对抗这种纤维化的一种尝试。 (C) 2004 年欧洲心脏病学会。由 Elsevier B.V 出版,保留所有权利。
Objective: Aging associated erectile dysfunction (ED) is primarily caused by the reduction in smooth muscle cells (SMC) and an increase in collagen within the corpora cavernosa, assumed to result from an increase in reactive oxygen species (ROS). This is accompanied by the expression of inducible nitric oxide synthase (NOS) to produce nitric oxide that scavenges ROS and inhibits collagen deposition. We investigated whether with aging similar processes occur within the arterial media SMC that share some common physiological functions with the cavernosal SMC. Methods: Aged (22-24 months) male Brown Norway rats received water with or without an inhibitor of NOS activity (L-N-(iminoethyl)-lysine acetate [L-NEL], 0.1 g/l), for 3 weeks. Young (3 months) untreated rats were used as control (n=5 per group). Tissue sections from the penis, abdominal aorta, femoral and brachial arteries were stained for collagen, SMC, NOS, ROS plasminogen activator inhibitor (PAI) and apoptosis, and evaluated by quantitative image analysis. ROS were also determined in fresh tissue and whole blood by the GSH/GSSG ratio. Results: It was observed that most aging-induced changes in the media of the arterial tree from the aorta to the resistance arteries in the penis are similar to what occurs in the corpora cavernosa, i.e. a decrease in the SMC/collagen ratio and an increase in ROS and NOS, and specifically in the case of the resistance arteries, an increase in SMC apoptosis and PAL NOS inhibition by L-NIL further increased ROS and decreased the SMC/collagen ratio in the media. Conclusions: These observations suggest that ED and arteriosclerosis in the aging male may share a common etiology, and that the expression of NOS by the SMC is an attempt to counteract this fibrosis. (C) 2004 European Society of Cardiology. Published by Elsevier B.V All rights reserved.