Nitric oxide (NO) is synthesized from L-arginine by nitric oxide synthase (NOS). NOS can be inhibited by NG-nitro-L-arginine methyl ester (L-NAME); and stimulated by supplementing the diet with L-arginine. The aim of this study was to investigate the influence of NOS activity on the response of rabbits to chronic partial bladder outlet obstruction (PBOO). Surgical PBOOs (2 and 8 weeks) were performed on male New Zealand White rabbits. Before obstruction, one third of the animals were premedicated for 7 days with L-NAME, and another third with L-arginine. The results are summarized as follows: 1) Bladder weight after 8 weeks PBOO was significantly lower in animals treated with L-arginine compared with both untreated and rabbits treated with L-NAME. 2) Contractile function decreased progressively with PBOO duration. However, after 8 weeks of PBOO, the L-arginine group had significantly greater contractile function compared to the no treatment group and the L-NAME group had significantly lower contractile function compared to the no treatment group. 3) At 8 weeks following PBOO, the level of protein oxidation and nitration was lowest for the L-arginine group and highest in the L-NAME group. These studies clearly demonstrated that increasing blood flow by stimulating NOS significantly protected the bladder from PBOO dysfunctions, whereas inhibiting blood flow by L-NAME enhanced the dysfunctions mediated by PBOO.