The correlation between nitric oxide and vascular endothelial growth factor in spinal cord injury

Spinal Cord. 2008 Feb;46(2):113-7. doi: 10.1038/ Epub 2007 Apr 10.


Study design: Prospective, randomized, placebo-controlled, experimental study.

Objectives: The issue of whether nitric oxide (NO) production is beneficial or deleterious on ischemic injuries of the central nervous system still remains doubtful. Vascular endothelial growth factor (VEGF) is known to induce the release of NO from endothelial cells. However, the effect of NO on VEGF synthesis is not clear. We aimed to determine the effects of L-arginine and NG-nitro-L-arginine methyl ester (L-NAME) on VEGF synthesis and free radicals in a rat model of spinal cord ischemia-reperfusion (IR) injury.

Setting: Surgical Research Laboratory of a Medical School.

Material and methods: Twenty-eight Wistar rats were divided into four groups as follows (n=7): Sham, IR injury, L-arginine, and L-NAME. Infrarenal abdominal aorta was occluded to induce spinal cord ischemia. L-Arginine (100 mg/kg) and L-NAME (10 mg/kg) were given before aortic occlusion. Biochemical assays of malondialdehyde (MDA), NO and VEGF were carried out in spinal cord specimens.

Results: L-Arginine treatment significantly increased MDA and NO, but decreased VEGF levels in spinal cord. However, nonselective inhibition of NOS with L-NAME significantly decreased MDA and NO, but increased VEGF levels. Besides, the positive linear correlation between MDA and NO, and negative linear correlations between MDA, NO and VEGF levels have also been demonstrated.

Conclusion: Nonselective inhibition of NO synthase activity with L-NAME attenuated free radical formation and increased VEGF level when compared with NO precursor L-arginine in a rat model of spinal cord ischemia. We suggest that inhibition of NO synthase, as well as induction of VEGF, may be a therapeutic option in spinal cord IR injury.

MeSH terms

  • Animals
  • Arginine / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Free Radicals / metabolism
  • Male
  • Malondialdehyde / metabolism
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase / drug effects
  • Rats
  • Rats, Wistar
  • Spinal Cord Injuries / metabolism*
  • Spinal Cord Injuries / physiopathology
  • Vascular Endothelial Growth Factor A / drug effects
  • Vascular Endothelial Growth Factor A / metabolism*


  • Enzyme Inhibitors
  • Free Radicals
  • Vascular Endothelial Growth Factor A
  • Nitric Oxide
  • Malondialdehyde
  • Arginine
  • Nitric Oxide Synthase
  • NG-Nitroarginine Methyl Ester