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 0.73 mg/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.