Regulation of NOS activity by the endogenous inhibitors and modification of hyperplastic vascular diseases with the inhibitors.

在项目期间，我们获得了以下结果：1。血浆浓度与吸烟者水平相当的尼古丁会通过增强对EDRF/NO生成的损害而加速内皮剥落后的内膜增生，这可能是由于LNMMA （N^G-单甲基- l-精氨酸）和ADMA （N^G， N^G-二甲基- l-精氨酸）浓度的增加（作为NO合成的抑制剂）和内皮素-1（血管壁中有效的丝裂原）的增加引起的。2.l -精氨酸内源性合成NO可能具有调节纤毛肌松弛的作用，在一定条件下细胞内甲基精氨酸浓度升高时，内源性ADMA可能参与抑制NO的生物合成。NO通过激活鸟苷酸环化酶和增加环GMP水平引起牛睫状肌松弛。3.ADMA作为一种内源性NO合成抑制剂，可能在嘌呤霉素氨基核苷酸致大鼠实验性局灶性和节段性肾小球硬化合并高血压的发病机制中起重要作用。4.增殖细胞核抗原和增殖细胞核标记物Ki-67的免疫组化结果显示，内膜增生期结束后平滑肌细胞进入静止状态时，弹力蛋白转录物和弹性蛋白形成增加，提示在动脉壁损伤修复过程中，弹性蛋白合成和平滑肌细胞增殖受到严格调控。5.兔球囊内皮脱落后新内膜中骨桥蛋白mRNA的表达与平滑肌细胞增殖有关。在动脉平滑肌细胞的原代培养中。骨桥蛋白mRNA在转入合成状态（G_<1B>， S和G_2 + M）的细胞中表达，而在收缩状态（G_<1A>期）或中间状态（G_<1A>期）的细胞中不表达，这表明骨桥蛋白mRNA的表达为区分血管平滑肌细胞的表型特性提供了有用的标记。6.p53蛋白和p53基因转录物水平的升高与增厚内膜中平滑肌细胞的增殖密切相关，在动脉壁损伤修复过程中对细胞增殖的调控起关键作用。少

During the term of project, we obtained the following results : 1.Nicotine at plasma concentrations corresponding to the levels of human smokers would accelerate the intimal hyperplasia after endothelial denudation through the enhanced impairment of the EDRF/NO production, which might be brought about by the enhanced increases in LNMMA (N^G-monomethyl-L-arginine) and ADMA (N^G, N^G-dimethyl-L-arginine) concentrations as inhibitors for NO synthesis, and the enhanced increase in endothelin-1 as a potent mitogen in the vessel wall. 2.The NO synthesized endogenously from L-arginine might play a role for mediating relaxation of the bovine ciliary muscle and that the endogenous ADMA might be involved in inhibiting the biosynthesis of NO when there are increased intracellular concentrations of the methylarginine under certain circumstances. NO causes relaxation of the bovine ciliary muscle through the activation of guanylate cyclase and an increase in cyclic GMP level. 3.ADMA as an endogenous … More inhibitor of NO synthesis may play an important role for the pathogenesis in the hypertension associated with the experimental focal and segmental glomerulosclerosis induced by puromycin aminonucleotide in the rat. 4.Immunohistochemistry for proliferating cell nuclear antigen and Ki-67, both markers for proliferating cell nuclei, showed that tropoelastin transcripts and elastin formation increased when smooth muscle cells enter quiescence after the end of the proliferative phase in the intima, suggesting that elastin synthesis and smooth muscle cell proliferation are tughtly regulated during the repair of arterial wall injury. 5.The expression of osteopontin mRNA in rabbit neointima after balloon endothelial denudation was associated with proliferating smooth muscle cells. In primary cultures of arterial smooth muscle cells.osteopontin mRNA was expressed in cells that had transferred to the synthetic state (G_<1B>, S and G_2 + M), and not in cells in either the contractile (G_0 phase) or intermediate states (G_<1A> phase), indicating that osteopontin mRNA expression provides a useful marker that can be applied to distiguish the phenotypic properties of vascular smooth muscle cells. 6.Increases in p53 protein and p53 gene transcript levels would be closely linked to the proliferation of smooth muscle cells in the thickened intima, and play a key role in the regulation of cell proliferation during the repair process after arterial wall injury. Less