Nitric oxide mediated vasoreactivity during fracture repair

An experimental model of fracture healing has been used to investigate whet her nitric oxide mediated vascular reactivity, determined using laser Doppl er flowmetry, is present in bone after a fracture. Times corresponding to D ays 0, 1, 3, 7, 14, and 28 after fracture were used to study the injured an d contralateral limbs in response to bolus intravenous administration of ni tric oxide inhibitor, N-nitro-L-arginine methyl ester, and nitric oxide sti mulator, acetylcholine. N-nitro-L-arginine methyl ester administration (1 m u mol/kg, 10 mu mol/kg, and 100 mu mol/kg) caused a dose dependent increase in systemic blood pressure each of the assessment groups; however, there w as no statistical difference between the groups. Doppler flow readings at t he fracture site showed measurable changes in local vascular reactivity aft er drug administration. At Day 1 after fracture, the magnitude of unit chan ge in vascular reactivity in response to N-nitro-L-arginine methyl ester (1 mu mol/kg, 10 mu mol/kg, and 100 mu mol/kg) was significantly higher in th e fractured limb compared with the contralateral limb and also when compare d with other points of assessment. These results show that nitric oxide med iated vasoreactivity is present about a fracture site and is maximal in the early healing phase, before returning to basal levels as healing progresse s. This is compatible with an initial restoration of blood flow at a fractu re site by nitric oxide dependent vasodilation of preexisting blood vessels , followed by ingrowth of less nitric oxide dependent angiogenic vessels du ring the later phase of repair.