Spontaneous recovery of injured Achilles tendon in inducible nitric oxide synthase gene knockout mice

Objective and Design: To determine if inducible nitric oxide synthase (iNOS) gene could affect Achilles tendon healing using iNOS gene knockout mice. Methods: 21 iNOS knockout (iNOS^−/−) mice and 8 of the wild type (iNOS^+/+) mice were utilized in this study. Group 1: iNOS^+/+ mice (n = 8), group 2: iNOS^−/− mice (n = 11) and group 3: iNOS^−/− with a NOS inhibitor, (aminoguanidine, 500 mg/kg/day, via an intraperitoneal mini-osmotic pump for 7 days, n = 10). The right Achilles tendon was transected in all mice and harvested on day 7 for cross-sectional area and biomechanical properties. Serum nitrate concentration of the mice was measured by gas chromatography mass spectrometry (GC/MS). Results: A significant reduction in cross-sectional area of the healing Achilles tendon was observed in group 3 mice compared to group 2 mice (p < 0.01). The serum nitrate concentration in both group 2 and group 3 mice was lower than that in group 1 mice (p < 0.01) iNOS gene deletion and inhibition of NOS did not affect the biomechanical properties of the healing tendons. Conclusions: iNOS gene is not solely responsible for the beneficial effects of nitric oxide (NO) on tendon healing. Received: 30 March 2005; returned for revision 4 August 2005; returned for final revision 27 September 2005; accepted by M. Parnham 28 September 2005