Up and down-regulation of phosphodiesterase-5 as related to tachyphylaxis and priapism
Abstract
PURPOSE: We identify whether tachyphylaxis and priapism effects of sildenafil are related to regulation of phosphodiesterase-5 (PDE-5) expression.
MATERIALS AND METHODS: Cavernous smooth muscle cells (CSMCs) were isolated from young rats and treated with 0, 1, 10 and 25 microM sildenafil with or without 100 microM of sodium nitroprusside for 3 and 7 days. The cells were subjected to reverse transcriptase-polymerase chain reaction and Western blot analysis for PDE-5 expression. Plasmid constructs carrying PDE-5A1 and PDE-5A2 promoters were transfected into COS-7 cells, treated with 25 microM sildenafil and analyzed for promoter activities. To simulate priapism, CSMCs were cultured under anoxia or hypoxia and then analyzed for PDE-5 expression. Furthermore, rats underwent bilateral pudendal arterial ligation for 1 day to 14 weeks, and corpus cavernous tissues were subjected to reverse transcriptase-polymerase chain reaction analysis for PDE-5 expression.
RESULTS: Up-regulation of PDE-5 was noted in CSMCs treated with 25 microM sildenafil for 7 days. PDE-5 messenger RNA and protein levels were significantly increased in the 7-day sildenafil treated cultures. Sodium nitroprusside appeared to down-regulate PDE-5 expression. Sildenafil significantly increased the activities of PDE-5A1 promoter. PDE-5 expression was significantly reduced under anoxia and hypoxia. The corpus cavernous tissue showed a gradual decrease in PDE-5 expression under ischemia.
CONCLUSIONS: Repeated…
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Evidence Hub reads this as a review, done in animal and cell cultures (in vitro), not in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health.
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