Journal of Toxicologic Pathology
Online ISSN : 1881-915X
Print ISSN : 0914-9198
ISSN-L : 0914-9198
Capillary Fenestration in N-butyl-N-(4-hydroxybutyl) nitrosamine-induced Rat Bladder Carcinoma is Promoted by Vascular Endothelial Growth Factor
Shin WakuiTomoko MutoHidetoshi OhshigeShinji SasakiRie OgasawaraSyunsuke MiyachiBungo FurusatoHiroyuki TakahashiToshio MasaokaHiroshi HanoMasakuni Furusato
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2000 Volume 13 Issue 4 Pages 219-224


Vascular endothelial growth factor (VEGF) is a dimeric glycoprotein that specifically increases vascular permeability and stimulates angiogenesis. Recently we demonstrated a high level of VEGF and VEGF mRNA expression in N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced rat bladder carcinomas with abundant fenestrated capillaries. We speculated that the expression of VEGF might be involved in the induction or maintenance of capillary fenestration, and examined ultrastructurally the morphological alteration of blood capillaries in BBN-induced rat bladder carcinoma following the administration of neutralizing antibody against VEGF. Five minutes after administration, the fenestrated endothelial cell ratio and the number of fenestrae decreased significantly, and continued to decrease with time reaching a minimum at 10 minutes after administration. The ratio thereafter gradually increased and at 30 minutes returned to its control condition. These results showed the specific inhibition of VEGF bioactivity potently induced to close the capillary fenestrations. We can suggest that VEGF synthesized by BBN-induced rat bladder carcinoma cells specifically induces and maintains the tumor capillary fenestrations.

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© 2000 The Japanese Society of Toxicologic Pathology
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