Roles of accumulated endogenous nitric oxide synthase inhibitors and decreased nitric oxide synthase activity for impaired trigonal relaxation with ischemia

Purpose: We examined whether endogenous nitric oxide (NO) synthase (NOS) inhibitors are involved in the impaired trigonal relaxation with ischemia in rabbits. Materials and Methods: Rabbits were divided into control and ischemia groups. Two weeks after partial vessel occlusion strips of trigone and detrusor were processed to determine endogenous methylarginines and L-arginine by automated high performance liquid chromatography. We also compared NOS activity and NO mediated functional responses to electrical field stimulation between 2 groups. Results: Neurogenic and NO but not sodium nitroprusside induced mediated relaxation in the trigone were significantly impaired following ischemia. Ca2+ dependent NOS activity, and baseline and stimulated cyclic guanosine monophosphate production with electrical field stimulation were significantly decreased following ischemia. The contents of L-NMMA (N-G-monomethyl-L-arginine) and asymmetrical ADMA (N-G, N-G-dimethyl-L-arginine) but not L-arginine or symmetrical SDMA (N-G, N'(G)-dimethyl-L-arginine) were increased in the trigone following ischemia. Authentic L-NMMA and ADMA but not SDMA inhibited neurogenic relaxations in a concentration dependent manner without affecting the relaxation produced by sodium nitroprusside in control tissue. Excess L-arginine abolished L-NMMA and ADMA inhibition. Conclusions: These results suggest that impaired NO mediated trigonal relaxation following ischemia is closely related to decreased NOS activity and the increased accumulation of L-NMMA and ADMA.