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

Biochem Biophys Res Commun. 2001 May 18;283(4):923-7.
Bivalacqua TJ, Hellstrom WJ, Kadowitz PJ, Champion HC.

Department of Urology, Tulane University School of Medicine, New Orleans, Louisiana, USA.

Nitric oxide (NO) is the principal mediator of penile erection. NO is synthesized by nitric oxide synthase (NOS). It has been well documented that the major causative factor contributing to erectile dysfunction in diabetic patients is the reduction in the amount of NO synthesis in the corpora cavernosa of the penis resulting in alterations of normal penile homeostasis. Arginase is an enzyme that shares a common substrate with NOS, thus arginase may downregulate NO production by competing with NOS for this substrate, l-arginine. The purpose of the present study was to compare arginase gene expression, protein levels, and enzyme activity in diabetic human cavernosal tissue. When compared to normal human cavernosal tissue, diabetic corpus cavernosum from humans with erectile dysfunction had higher levels of arginase II protein, gene expression, and enzyme activity. In contrast, gene expression and protein levels of arginase I were not significantly different in diabetic cavernosal tissue when compared to control tissue. The reduced ability of diabetic tissue to convert l-arginine to l-citrulline via nitric oxide synthase was reversed by the selective inhibition of arginase by 2(S)-amino-6-boronohexanoic acid (ABH). These data suggest that the increased expression of arginase II in diabetic cavernosal tissue may contribute to the erectile dysfunction associated with this common disease process and may play a role in other manifestations of diabetic disease in which nitric oxide production is decreased. Copyright 2001 Academic Press.11350073 [PubMed - indexed for MEDLINE]

• Roles of attenuated neuronal nitric-oxide synthase protein expression and accelerated arginase activity in impairing neurogenic relaxation of corpus cavernosum in aged rabbits.
• Overexpression of arginase in the aged mouse penis impairs erectile function and decreases eNOS activity: influence of in vivo gene therapy of anti-arginase.
• Endothelial nitric oxide synthase protein expression, localization, and activity in the penis of the alloxan-induced diabetic rat.
• [Effect of aging on the expression of nitric oxide synthase I and the activity of nitric oxide synthase in the rat penis]
• Adenoviral gene transfer of endothelial nitric oxide synthase (eNOS) to the penis improves age-related erectile dysfunction in the rat.