Increased expression of arginase II in human diabetic corpus cavernosum: In diabetic-associated erectile dysfunction

Nitric oxide (NO) is the principal mediator of penile erection. NO is synth esized by nitric oxide synthase (NOS). It has been well documented that the major causative factor contributing to erectile dysfunction in diabetic pa tients is the reduction in the amount of NO synthesis in the corpora cavern osa of the penis resulting in alterations of normal penile homeostasis, Arg inase is an enzyme that shares a common substrate with NOS, thus arginase m ay downregulate NO production by competing with NOS for this substrate, L-a rginine. The purpose of the present study was to compare arginase gene expr ession, protein levels, and enzyme activity in diabetic human cavernosal ti ssue, When compared to normal human cavernosal tissue, diabetic corpus cave rnosum from humans with erectile dysfunction had higher levels of arginase II protein, gene expression, and enzyme activity. In contrast, gene express ion and protein levels of arginase I were not significantly different in di abetic cavernosal tissue when compared to control tissue. The reduced abili ty of diabetic tissue to convert L-arginine to L-citrulline via nitric oxid e synthase was reversed by the selective inhibition of arginase by 2(S)-ami no-6-boronohexanoic acid (ABH). These data suggest that the increased expre ssion of arginase II in diabetic cavernosal tissue may contribute to the er ectile dysfunction associated with this common disease process and may play a role in other manifestations of diabetic disease in which nitric oxide p roduction is decreased. (C) 2001 Academic Press.