期刊名称：Journal of Clinical Biochemistry and Nutrition
印刷版ISSN：0912-0009
电子版ISSN：1880-5086
出版年度：2006
卷号：38
期号：2
页码：95-102
DOI：10.3164/jcbn.38.95
出版社：The Society for Free Radical Research Japan
摘要：We investigated the influence of inducible nitric oxide synthase (iNOS) on acute ischemic injury and chronic angiogenesis. In a hindlimb ischemia model, NO produced by endothelial NO synthase (eNOS) reduces ischemic injury and promotes angiogenesis. However, the effect of the large amounts of NO generated by induced iNOS is unclear. Experimental groups of mice were as follows: (1) wild-type group (Wild), (2) iNOS-knockout group (iNOS-KO), and (3) aminoguanidine-treated wild-type group (Wild + AG), which received aminoguanidine from day 0 to day 3 after ischemia. Acute ischemic injury was evaluated by measuring the plasma CK value and ischemic score. Chronic angiogenesis was evaluated by microangiography and with a non-contact type Doppler blood flowmeter on day 3. Compared with the Wild group (251 ± 34.7 IU/l), the CK value was significantly elevated in the iNOS-KO (497 ± 126.7 IU/l) and Wild + AG (587.2 ± 128.7 IU/l) groups. The ischemic score was significantly increased in the iNOS-KO (92%) and Wild ± AG (66.6%) groups compared with the Wild group (23%). Blood flow was significantly increased in the iNOS-KO group (58.7 ± 15.3%) compared with the Wild (38.1 ± 15.9%) and Wild ± AG (43.5 ± 9.8%) groups in the chronic stage. Microangiography revealed a significantly increased number of blood vessels in the iNOS-KO (0.29 ± 0.02) group compared with the Wild (0.12 ± 0.01) and Wild + AG (0.15 ± 0.02) groups. Our findings indicate that NO generated by iNOS has a biphasic action, reducing acute ischemic injury and inhibiting angiogenesis in the chronic stage.
