Involvement of increased arginase activity in impaired cavernous relaxation with aging in the rabbit

Purpose: Arginase shares L-arginine as a common substrate with nitric oxide (NO) synthase (NOS). We examined whether increased arginase activity is involved in impaired cavernous relaxation with aging in the rabbit. Materials and Methods: Young adult (3 to 5 months old) and aged (36 to 48 months old) rabbits were used for the current experiments. Cavernous tissues obtained from the 2 groups were processed for isometric tension experiments, cyclic guanosine monophosphate determination, measurements of NOS and arginase activities, endogenous methylarginines and L-arginine. Results: Carbachol (CCh) produced an endothelium dependent and NO mediated relaxation that was significantly impaired in aged cavernous specimens without change in sodium nitroprusside induced relaxation. Stimulated cyclic guanosine monophosphate production with CCh was significantly decreased in aged cavernous specimens. Ca2+ dependent NOS was predominant in rabbit cavernous specimens. Ca2+ dependent and independent NOS activities remained unchanged in the 2 groups. The tissue contents of N-G-monomethyl-L-arginine and asymmetric N-G, N-G-dimethyl-L-arginine as endogenous NOS inhibitors, symmetrical N-G,N-G-dimethyl-L-arginine and L-arginine as a substrate of NOS were decreased in aged cavernous specimens. Arginase activity was significantly higher in aged cavernous specimens. Impaired CCh induced ;relaxation in aged cavernous specimens was normalized in the presence of N-G-hydroxy-L-arginine as an arginase inhibitor or by the supplementation of excess L-arginine. Conclusions: These results strongly suggest that impaired endothelium dependent and NO mediated cavernous relaxation with aging is due to decreased NO production, which would result from increased arginase activity and probably from decreased L-arginine content.