Tomita H, Egashira K, Kubo-Inoue M, Usui M, Koyanagi M, Shimokawa H, Takeya M, Yoshimura T, Takeshita A
Research Institute of Angiocardiology, Kyushu University Faculty of Medicine, Fukuoka, Japan.
Arterioscler Thromb Vasc Biol. 1998 Sep;18(9):1456-64. doi: 10.1161/01.atv.18.9.1456.
We recently showed that chronic inhibition of NO synthesis by N(omega)-nitro-L-arginine methyl ester (L-NAME) causes coronary vascular remodeling (ie, vascular fibrosis and medial thickening) in rats. To test the hypothesis that the inhibition of NO synthesis induces inflammatory changes in the heart, we characterized the inflammatory lesions that occurred during L-NAME administration and determined whether inflammation involved the induction of monocyte chemoattractant protein-1 (MCP-1) in vivo. During the first week of L-NAME administration to Wistar-Kyoto rats, we observed a marked infiltration of mononuclear leukocytes (ED1-positive macrophages) and fibroblast-like cells (alpha-smooth muscle actin-positive myofibroblasts) into the coronary vessels and myocardial interstitial areas. These inflammatory changes were associated with the expression of proliferating cell nuclear antigen and MCP-1 (both mRNA and protein). The areas affected by inflammatory changes, as well as the expression of MCP-1 mRNA, declined after longer (28 days) treatment with L-NAME and were replaced by vascular and myocardial remodeling. Our results support the hypothesis that the inhibition of NO synthesis induces inflammatory changes in coronary vascular and myocardial tissues and involves MCP-1 expression. Results also suggest that the early stages of inflammatory changes are important in the development of later-stage structural changes observed in rat hearts.
我们最近发现，用N（ω）-硝基-L-精氨酸甲酯（L-NAME）长期抑制一氧化氮合成会导致大鼠冠状动脉血管重塑（即血管纤维化和中层增厚）。为了验证一氧化氮合成抑制会诱发心脏炎症变化这一假说，我们对L-NAME给药期间出现的炎症病变进行了特征描述，并确定炎症在体内是否涉及单核细胞趋化蛋白-1（MCP-1）的诱导。在对Wistar-Kyoto大鼠给予L-NAME的第一周，我们观察到单核白细胞（ED1阳性巨噬细胞）和成纤维细胞样细胞（α-平滑肌肌动蛋白阳性肌成纤维细胞）显著浸润到冠状血管和心肌间质区域。这些炎症变化与增殖细胞核抗原和MCP-1（mRNA和蛋白）的表达相关。在用L-NAME进行更长时间（28天）治疗后，受炎症变化影响的区域以及MCP-1 mRNA的表达下降，并被血管和心肌重塑所取代。我们的结果支持以下假说：一氧化氮合成的抑制会诱发冠状血管和心肌组织的炎症变化，并涉及MCP-1的表达。结果还表明，炎症变化的早期阶段在大鼠心脏后期观察到的结构变化发展中很重要。
