The present study investigates the potential of tadalafil, a phosphodiesterase-5 inhibitor, in a rat model of hyperhomocysteinemia induced vascular dementia. Hyperhomocysteinemia induced vascular dementia in Wistar rats was produced by administering L-Methionine (1.7g/kg/day; p.o. x 8 weeks). Learning and memory was assessed by employing Morris water maze (MWM) test. Endothelial dysfunction was assessed through acetylcholine-induced endothelial-dependent vasorelaxation and serum nitrite levels. Various other biochemical and histopathological estimations were also performed. L-Methionine produced significant impairment in acetylcholine-induced endothelium-dependent vasorelaxation and a decrease in serum nitrite levels indicating endothelial dysfunction. Further, these animals performed poorly on Morris water maze, depicting impairment of learning and memory. There was a significant rise in brain oxidative stress level (indicated by an increase in brain thiobarbituric acid reactive species and a decrease in reduced glutathione levels). Increase in brain acetylcholinesterase activity; brain myeloperoxidase activity and brain neutrophil infiltration (a marker of inflammation) were also observed. Tadalafil (5 & 10 mg/kg, p.o.)/donepezil (0.5 mg/kg, i.p., serving as standard) treatment ameliorated L-Methionine induced endothelial dysfunction; memory deficits; biochemical and histopathological changes in a significant manner. It may be concluded that tadalafil has shown efficacy in the rat model of L-Methionine induced vascular dementia and that phosphodiesterase-5 can be considered as an important therapeutic target for the treatment of vascular dementia.

本研究调查了高同型半胱氨酸血症诱发的血管性痴呆大鼠模型中他达拉非（一种磷酸二酯酶5抑制剂）的潜力。Wistar大鼠高同型半胱氨酸血症诱发的血管性痴呆是通过施用L-蛋氨酸（1.7g / kg /天；口服x 8周）产生的。通过使用莫里斯水迷宫（MWM）测试评估学习和记忆。通过乙酰胆碱诱导的内皮依赖性血管舒张和血清亚硝酸盐水平评估内皮功能障碍。还进行了其他各种生化和组织病理学评估。L-蛋氨酸在乙酰胆碱诱导的内皮依赖性血管舒张中产生了明显的损伤，并且血清亚硝酸盐水平的降低表明了内皮功能障碍。此外，这些动物在莫里斯水迷宫中的表现较差，描述学习和记忆障碍。脑氧化应激水平显着升高（通过脑中硫代巴比妥酸反应性物种的增加和谷胱甘肽水平降低的减少来表明）。增加脑中乙酰胆碱酯酶的活性；还观察到脑髓过氧化物酶活性和脑中性粒细胞浸润（炎症的标志）。他达拉非（5＆10 mg / kg，口服）/多奈哌齐（0.5 mg / kg，腹腔注射，作为标准）治疗改善了L-蛋氨酸诱导的内皮功能障碍; 记忆力减退; 生化和组织病理学改变有重大意义。可以得出结论，他达拉非在L-蛋氨酸诱导的血管性痴呆大鼠模型中显示出功效，并且磷酸二酯酶5可以被认为是治疗血管性痴呆的重要治疗靶点。