Abstract
Background: Sildenafil is a potent and selective inhibitor of cyclic guanosine monophosphate -specific phosphodiesterase type 5 that results in arterial vasodilation. Thus, sildenafil has been proposed as an alternative treatment of Persistent Pulmonary Hypertension of the Newborn. However, very little is known on the adverse effects of sildenafil, specifically on the CNS. Its administration enhances functional recovery and increases neurogenesis and vasculogenesis in the adult rat after stroke. In the developing brain the effects of sildenafil remain unknown.
Objective: To determine the effect of sildenafil on vasculogenesis after hypoxic injury in a rat pup model.
Design/Methods: Sixteen male Wistar rat pups were randomly assigned at P10 to receive Sildenafil 5 mg/kg/day or sterile water three hours before being subjected to hypoxic conditions. All animal were exposed to FiO2 of 10.4% for 10 minutes. On P25 animals were euthanized, brains removed fixed, and paraffin embedded. Immunohistochemistry using anti VEGF antibody was performed, VEGF positive cells were counted in 16 fields in three different slides for each animal. Results were expressed as mean± SD.
Results: All animals survived the experimental conditions. There was no significant difference in the number of VEGF- positive cells between control and sildenafil-treated pups (254 ±31 cells vs. 273 ± 26 cells, respectively).
Conclusions: In our animal model of hypoxic injury of the developing brain, sildenafil does not seem to have a significant effect on vasculogenesis as determined by VEGF expression. Further assessment of vasculogenesis by other methods and /or under different conditions is needed.
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Nirapil, J., Aguirre, N., Rogido, M. et al. 581 Effect of Sildenafil on Vegf Expression in the Postnatal Murine Brain After Hypoxemic Injury. Pediatr Res 68 (Suppl 1), 298 (2010). https://doi.org/10.1203/00006450-201011001-00581
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DOI: https://doi.org/10.1203/00006450-201011001-00581
