Introduction: Cerebral hypoperfusion has been considered as major risk factor for Vascular
Dementia (VaD). The present study shows the potential of Tadalafil, a phosphodiesterase-5
inhibitor, in bilateral common carotid artery occlusion (BCCAo) induced VaD in rats.
Materials and Methods: BCCAo procedure was performed under anesthesia in wistar rats to induce
VaD. Morris Water-Maze (MWM) parameter was employed on 7th day post-surgery to determine
learning and memory. Escape latency time, time spent in target quadrant, Path length and
average swim speed taken as important parameters in MWM. Endothelial dysfunction was assessed
in isolated aorta by observing endothelial dependent vasorelaxations and levels of serum
nitrite. Various biochemical and histopathological estimations were also performed.
Results: BCCAo produced significant impairment in endothelium dependent vasorelaxation and a
decrease in serum nitrite levels indicating endothelial dysfunction. Further poor performance on
MWM represents impairment of learning and memory. There was a significant rise in brain oxidative
stress level (indicated by increase in brain thiobarbituric acid reactive species and decrease in
reduced glutathione levels). Increase in brain acetylcholinesterase activity; brain myloperoxidase
activity and brain neutrophil infiltration (as marker of inflammation) were also observed.
Treatment of Tadalafil (5 & 10 mg/kg, p. o.)/Donepezil (0. 5 mg/kg, i.p., serving as standard)
ameliorated BCCAo induced endothelial dysfunction; memory deficits; biochemical and
histopathological changes in a significant manner.
Conclusion: It may be concluded that Tadalafil has shown efficacy in rat model of BCCAo induced
VaD and that phosphodiesterase-5 can be considered as an important therapeutic target for
the treatment of VaD.