The relationship between venous hypertension and expression of vascular endothelial growth factor: hemodynamic and immunohistochemical examinations in a rat venous hypertension model

Surg Neurol. 2007 Sep;68(3):277-84; discussion 284. doi: 10.1016/j.surneu.2006.10.075.


Background: Venous hypertension is regarded as an important factor in the pathogenesis of dural arteriovenous fistula (DAVF). We investigate histologic reaction of dural sinus under the condition of venous hypertension using a rat venous hypertension model to present hemodynamic and immunohistochemical effect in the development of DAVF.

Methods: Twenty-four Sprague-Dawley male rats were divided into venous hypertension and control groups. Venous hypertension was induced with a left common carotid artery-external jugular vein anastomosis and an occlusion of a right posterior facial vein. Measurements of systemic mean arterial pressure, draining vein pressure (DVP), and cerebral perfusion pressure (CPP) were conducted on the next day, at 7 days, and at 28 days after surgery, and the rats were killed for histologic examinations.

Results: Postoperative DVP increased significantly in venous hypertension group compared to control group (35 +/- 5 vs 13 +/- 2 mm Hg, P < .05). Increased DVP remained above 30 mm Hg throughout the observation period. Postoperative CPP decreased significantly in venous hypertension group compared to control group (49 +/- 8 vs 86 +/- 9 mm Hg, P < .05). In venous hypertension group, there was a significant difference between days 1 and 28 (49 +/- 8 vs 64 +/- 8 mm Hg, P < .05). Histologic examination revealed thickening of connective tissues, proliferation of fibroblasts, and strong expression of vascular endothelial growth factor (VEGF) in endothelium under venous hypertension condition. Immunostained VEGF cells decreased significantly from day 7 to day 28 (100 +/- 16 vs 72 +/- 19 cells, P < .05). A positive correlation was observed between DVP and VEGF expression (Pearson correlation coefficient; r = 0.671, P = .0017). There was a negative correlation between CPP and immunostained VEGF cells (r = -0.702, P = .0089).

Conclusions: These results suggest that venous hypertension is associated with increased expression of VEGF, and a decreased CPP may have a potential effect in VEGF expression under venous hypertension condition. These factors are speculated to play an important role in progression of DAVF.

MeSH terms

  • Animals
  • Central Nervous System Vascular Malformations / etiology*
  • Cerebrovascular Circulation / physiology
  • Cranial Sinuses / metabolism*
  • Cranial Sinuses / pathology*
  • Cranial Sinuses / physiopathology
  • Disease Models, Animal
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors
  • Vascular Endothelial Growth Factor A / metabolism*
  • Venous Pressure / physiology*


  • Vascular Endothelial Growth Factor A