Key result
In a mouse hindlimb ischemia model, iNOS deficiency significantly increased acute ischemic injury (CK 497 vs 251 IU/l) but enhanced chronic angiogenesis compared to wild-type mice.
Why the study?
Does iNOS knockout or inhibition affect acute ischemic injury and chronic angiogenesis in a mouse hindlimb ischemia model?
Does iNOS knockout or inhibition affect acute ischemic injury and chronic angiogenesis in a mouse hindlimb ischemia model?
Absolute Event Rate: 497% vs 251%
p-value: p=<0.05
iNOS exhibits a biphasic action in hindlimb ischemia, reducing acute ischemic injury but inhibiting angiogenesis in the chronic stage.
Mouse data preclude iNOS inhibition in acute ischemia; leaves open stage-specific angiogenesis modulation.
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.
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Kimura et al. (2006) studied Hindlimb ischemia. iNOS knockout or aminoguanidine treatment vs. Wild-type mice was evaluated on Serum CK value on day 3 (acute ischemic injury) (p=<0.05). In a mouse hindlimb ischemia model, iNOS deficiency significantly increased acute ischemic injury (CK 497 vs 251 IU/l) but enhanced chronic angiogenesis compared to wild-type mice.