N (G)-nitro-L- arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, diminishes oxidative damage in urinary bladder partial outlet obstruction

Partial bladder outlet obstruction (PBOO) results in cellular damage due to ischemia and reperfusion injury. Our study seeks to establish how early this damage can occur, and the role that nitric oxide may play in its pathophysiology. Surgical partial bladder outlet obstructions (1, 3, and 7 days) were performed on male New Zealand white rabbits. Half of the animals were pre-medicated for 3 days with L-NAME, an inhibitor of nitric oxide synthase prior to obstruction. Bladder weight increased with duration of PBOO, but was significantly lower at 3 and 7 days in animals treated with L-NAME as compared to their untreated counterparts. Contractile function decreased progressively with PBOO duration. At 1-day post obstruction, bladder contractility was significantly lower in the L-NAME rabbits than in the untreated rabbits. At 3 and 7 days, contractility of the L-NAME bladders was equal or higher than the untreated bladders. The level of hypoxia at 1 day following obstruction was significantly higher in the L-NAME treated animals than in the untreated controls, but equal at 3 and 7 days obstruction. Increased nitrotyrosine was seen by Western blot in all obstructed animals. However, the amount was significantly less in the L-NAME treated animals at 3 and especially 7 days. Nerve density decreased progressively following obstruction; however, it decreased to a significantly lesser degree in the L-NAME treated bladders than in the untreated groups. These results suggest that L-NAME pretreatment enhanced ischemic damage at 1 day following obstruction; but protected the bladder from NO generated free radical damage at the later time periods by inhibiting the generation of nitrotyrosine.