Effect of the phosphodiesterase-5 inhibitor zaprinast on ischemia-reperfusion injury in rats.

Purpose: The cardiac and renal protective effects of phosphodiesterase-5 (PDE-5) inhibitors against ischemia-reperfusion injury have recently been demonstrated in animal studies. We evaluated the effect of pretreatment with the PDE-5 inhibitor zaprinast on warm renal ischemia in a rat model. Methods: Female Sprague-Dawley rats underwent concomitant right nephrectomy and left renal hilar occlusion for 30 minutes. Twelve animals were equally divided into three groups: Group 1 received no pharmacologic pretreatment, group 2 was pretreated with zaprinast 10 mg/kg, and group 3 was pretreated with zaprinast 20 mg/kg. Zaprinast was dissolved in 25% dimethyl sulfoxide and given as a single intraperitoneal injection 30 minutes before surgery. Serum blood urea nitrogen (BUN) and creatinine levels, histopathology, and TUNEL staining for apoptosis were assessed 24 hours postoperatively. Results: The mean creatinine level for groups 1, 2, and 3 was 0.73mg/dL, 0.55 mg/dL, and 0.38 mg/dL, respectively. These values were not statistically different (P = 0.099). The mean BUN levels of 35.8 mg/dL for group 1, 27.3 mg/dL for group 2, and 23.3 mg/dL for group 3 were also statistically similar (P = 0.278). There were no objective differences in histopathologic evaluation or TUNEL staining between the groups. Conclusion: This study did not demonstrate a beneficial effect of zaprinast pretreatment on renal parameters after warm ischemic injury.