Nitric oxide mediated vasoreactivity during fracture repair

Clin Orthop Relat Res. 1999 Aug;(365):247-53. doi: 10.1097/00003086-199908000-00030.


An experimental model of fracture healing has been used to investigate whether nitric oxide mediated vascular reactivity, determined using laser Doppler flowmetry, is present in bone after a fracture. Times corresponding to Days 0, 1, 3, 7, 14, and 28 after fracture were used to study the injured and contralateral limbs in response to bolus intravenous administration of nitric oxide inhibitor, N-nitro-L-arginine methyl ester, and nitric oxide stimulator, acetylcholine. N-nitro-L-arginine methyl ester administration (1 mumol/kg, 10 mumol/kg, and 100 mumol/kg) caused a dose dependent increase in systemic blood pressure in each of the assessment groups; however, there was no statistical difference between the groups. Doppler flow readings at the fracture site showed measurable changes in local vascular reactivity after drug administration. At Day 1 after fracture, the magnitude of unit change in vascular reactivity in response to N-nitro-L-arginine methyl ester (1 mumol/kg, 10 mumol/kg, and 100 mumol/kg) was significantly higher in the fractured limb compared with the contralateral limb and also when compared with other points of assessment. These results show that nitric oxide mediated vasoreactivity is present about a fracture site and is maximal in the early healing phase, before returning to basal levels as healing progresses. This is compatible with an initial restoration of blood flow at a fracture site by nitric oxide dependent vasodilation of preexisting blood vessels, followed by ingrowth of less nitric oxide dependent angiogenic vessels during the later phase of repair.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / administration & dosage
  • Acetylcholine / pharmacology
  • Animals
  • Blood Pressure / drug effects
  • Bone and Bones / blood supply*
  • Bone and Bones / drug effects
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / administration & dosage
  • Enzyme Inhibitors / pharmacology
  • Follow-Up Studies
  • Fracture Healing / drug effects*
  • Injections, Intravenous
  • Laser-Doppler Flowmetry
  • Male
  • NG-Nitroarginine Methyl Ester / administration & dosage
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Neovascularization, Physiologic / physiology
  • Nitric Oxide / administration & dosage
  • Nitric Oxide / antagonists & inhibitors
  • Nitric Oxide / pharmacology*
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Rats
  • Rats, Wistar
  • Regional Blood Flow / physiology
  • Vasodilator Agents / administration & dosage
  • Vasodilator Agents / antagonists & inhibitors
  • Vasodilator Agents / pharmacology*


  • Enzyme Inhibitors
  • Vasodilator Agents
  • Nitric Oxide
  • Nitric Oxide Synthase
  • Acetylcholine
  • NG-Nitroarginine Methyl Ester