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Updated: Aug 24, 2026
Induction of Myocardial Infarction and Myocardial Ischemia-Reperfusion Injury in Mice
Published on: January 19, 2022
Reperfusion injury in skeletal muscle is reduced in inducible nitric oxide synthase knockout mice
Wen-Ning Qi1, Long-En Chen, Li Zhang
1Orthopaedic Research Laboratory, Duke Univ. Medical Center, Box 3093, Durham, NC 27710, USA.
Abstract:
Inducible nitric oxide synthase (iNOS) participates in many pathological events, and selective inhibition of iNOS has been shown to reduce ischemia-reperfusion (I/R) injury in different tissues. To further confirm its role in this injury process, I/R injury was observed in denervated cremaster muscles of iNOS-deficient (iNOS-/-) and wild-type mice. After 3-h ischemia and 90-min reperfusion, blood flow in reperfused muscle was 80 +/- 8.5% (mean +/- SE) of baseline at 10-min reperfusion and completely returned to the preischemia baseline after 20 min in iNOS-/- mice. In contrast, blood flow was 32 +/- 7.4% at 10 min and increased to 60 +/- 20% of the baseline level at 90 min in wild-type mice (P < 0.001 vs. iNOS-/- mice at all time points). The increased muscle blood flow in iNOS-/- mice was associated with significantly less vasospasm in all three sizes of arterial vessel size categories. The weight ratio to the contralateral muscle not subjected to I/R was greater in wild-type mice (173 +/- 11%) than in iNOS-/- mice (117 +/- 3%; P < 0.01). Inflammation and neutrophil extravasation were also more severe in wild-type mice. Western blot analysis demonstrated an absence of iNOS protein band in iNOS-/- mice and upregulation of iNOS protein expression in wild-type mice. Our results confirm the importance of iNOS in I/R injury. Upregulated iNOS exacerbates I/R injury and appears to be a therapeutic target in protection of tissues against this type of injury.
Insights
Inducible nitric oxide synthase (iNOS) exacerbates ischemia-reperfusion (I/R) injury. Inhibiting iNOS in mice significantly improved blood flow recovery and reduced tissue damage after I/R, highlighting its therapeutic potential.
Area of Science:
- Physiology
- Pathology
- Immunology
Background:
- Inducible nitric oxide synthase (iNOS) plays a role in various pathological conditions.
- Selective iNOS inhibition has shown promise in mitigating ischemia-reperfusion (I/R) injury across different tissues.
Purpose of the Study:
- To investigate the specific role of iNOS in the pathogenesis of I/R injury.
- To evaluate the impact of iNOS deficiency on microvascular function and tissue damage following I/R.
Main Methods:
- Ischemia-reperfusion (I/R) injury was induced in denervated cremaster muscles of iNOS-deficient (iNOS-/-) and wild-type mice.
- Post-ischemic blood flow recovery, vasospasm, muscle weight changes, and inflammatory markers were assessed.
- Western blot analysis was used to confirm iNOS protein expression levels.
Main Results:
- iNOS-/- mice exhibited significantly faster and more complete blood flow recovery (80% at 10 min) compared to wild-type mice (32% at 10 min).
- Reduced vasospasm, less severe inflammation, and lower neutrophil extravasation were observed in iNOS-/- mice.
- Wild-type mice showed greater muscle weight gain, indicative of more severe edema, compared to iNOS-/- mice.
Conclusions:
- The results confirm that inducible nitric oxide synthase (iNOS) plays a critical role in exacerbating ischemia-reperfusion (I/R) injury.
- Upregulated iNOS contributes to impaired microvascular function and increased tissue damage post-I/R.
- Targeting iNOS represents a potential therapeutic strategy for protecting tissues against I/R-induced injury.
