Arthur J F, Yin Z L, Young H M, Dusting G J
Department of Physiology, University of Melbourne, Parkville, Victoria, Australia.
Arterioscler Thromb Vasc Biol. 1997 Apr;17(4):737-40. doi: 10.1161/01.atv.17.4.737.
A Silastic collar placed around the common carotid artery of rabbits causes the formation, within 7 days, of an atheroma-like neointima containing cells with the appearance of synthetic-phenotype smooth muscle cells. Using immunohisto-chemistry, we detected the appearance of the cytokine-inducible form of nitric oxide synthase (iNOS, or isoform II) in the neointima of rabbits that had the collar in place for 7 or 14 days. This iNOS immunofluorescence collocalized with anti-smooth muscle myosin in the intima, indicating that it is expressed in smooth muscle cells, and iNOS was also present in a few endothelial cells in collared sections. There was no evidence of iNOS expression in the arterial wall before the neointima was apparent, that is, after only 2 days with the collar. The expression of endothelial NOS (eNOS, or isoform III) immunofluorescence was confined to the endothelial cells in control sections, as it was in collared sections with neointima at 7 and 14 days. Specific immunofluorescence for neuronal NOS (nNOS, or isoform I) was not observed in any sections. Our results suggest that nitric oxide is produced by the inducible isoform of NOS in modified smooth muscle cells of the developing neointima. Activity of iNOS might deprive the endothelium of substrate for nitric oxide production and might explain the compromised endothelium-dependent vasodilatation observed both in this model of atherosclerosis and in human coronary artery disease.
在兔颈总动脉周围放置一个硅橡胶套环，7天内会形成一种动脉粥样瘤样新生内膜，其中含有具有合成表型平滑肌细胞外观的细胞。利用免疫组织化学方法，我们在套环放置7天或14天的兔新生内膜中检测到细胞因子诱导型一氧化氮合酶（iNOS，即同工型II）的出现。这种iNOS免疫荧光在内膜中与抗平滑肌肌球蛋白共定位，表明它在平滑肌细胞中表达，并且在套环处理的切片中的一些内皮细胞中也存在iNOS。在新生内膜出现之前，即在套环放置仅2天后，动脉壁中没有iNOS表达的证据。内皮型一氧化氮合酶（eNOS，即同工型III）免疫荧光的表达在对照切片中局限于内皮细胞，在7天和14天有新生内膜的套环处理切片中也是如此。在任何切片中均未观察到神经元型一氧化氮合酶（nNOS，即同工型I）的特异性免疫荧光。我们的结果表明，一氧化氮是由发育中的新生内膜中经修饰的平滑肌细胞中的诱导型一氧化氮合酶产生的。iNOS的活性可能会剥夺内皮细胞产生一氧化氮的底物，这可能解释了在这种动脉粥样硬化模型和人类冠状动脉疾病中观察到的内皮依赖性血管舒张功能受损的现象。
