Abstract:
Objective: It has been reported that phosphodiesterase-5 (PDE5) inhibitors improve kidney functions during acute and chronic renal failure. This study aimed to determine the possible therapeutic effects of tadalafil, a specific PDE5 inhibitor, on renal fibrosis induced by unilateral ureteral obstruction (UUO).
Methods: Male Sprague-Dawley rats were used and randomly divided into three groups (n=6) as sham-operated, UUO and tadalafil-treated (10 mg/72 h, ig) UUO (UUO+T) groups. UUO was induced by complete ligation of the left ureter and 14 days after surgery creatinine clearance, urinary cGMP, renal a-sma and TGF-β levels, as well as histologic changes, were observed in all animals.
Results: UUO-induced renal fibrosis was confirmed by increased a-sma level, collagen deposition, tubular dilation, inflammatory cell infiltration and necrosis. An increased renal TGF-β level and decreased urinary cGMP level was also observed in obstructed animals in addition to reduced creatinine clearance. Tadalafil treatment, which restored urinary cGMP level, significantly attenuated the fibrotic changes and TGF-β increase in kidneys.
Conclusion: This study suggests that tadalafil treatment ameliorates renal fibrosis by reducing TGF-β expression and may have important clinical relevance since tadalafil is currently used clinically to treat erectile dysfunction and pulmonary hypertension.