Chronic Oral Administration of the Arginase Inhibitor 2(S)‐amino‐6‐boronohexanoic Acid (ABH) Improves Erectile Function in Aged Rats

• Published in: Journal of andrology 2012-11, Vol.33 (6), p.1169-1175
• Main Authors: Segal, Robert, Hannan, Johanna L., Liu, Xiaopu, Kutlu, Omer, Burnett, Arthur L., Champion, Hunter C., Kim, Jae Hyung, Steppan, Jochen, Berkowitz, Dan E., Bivalacqua, Trinity J.
• Format: Article
• Language: English
• Subjects: Administration, Oral; aging; Aging - physiology; Aminocaproates - administration & dosage; Aminocaproates - therapeutic use; Animals; Arginase; Biological and medical sciences; Boron Compounds - administration & dosage; Boron Compounds - therapeutic use; Electric Stimulation; Enzyme Inhibitors - administration & dosage; Enzyme Inhibitors - therapeutic use; Erectile dysfunction; Erectile Dysfunction - drug therapy; Fundamental and applied biological sciences. Psychology; Gynecology. Andrology. Obstetrics; Male; Male genital diseases; Mammalian male genital system; Medical sciences; nitric oxide; penile erection; Penile Erection - physiology; Penis - enzymology; Penis - innervation; Rats; Rats, Inbred F344; Vertebrates: reproduction
• ISSN: 0196-3635; 1939-4640
• DOI: 10.2164/jandrol.111.015834

: Arginase expression and activity have been noted to be heightened in conditions associated with erectile dysfunction, including aging. Previously, arginase inhibition by chronic administration of the arginase inhibitor 2‐(S)‐amino‐6‐boronohexanoic acid (ABH) has been shown to improve endothelial dysfunction in aged rats. The objective of this study was to assess whether chronic oral ABH administration affects cavernosal erectile function. Rats were divided into 4 groups: young control, young treated with arginase inhibitor, aged control, and aged treated with arginase inhibitor. Arginase activity was measured and presented as a proportion of young untreated rats. In vivo erectile responses to cavernous nerve stimulation were measured in all cohorts. The cavernous nerve was stimulated with a graded electrical stimulus, and the intracavernosal/mean arterial pressure ratios and total intracavernosal pressure were recorded. Arginase activity was elevated in the aged rats compared with young controls; however, arginase activity was significantly decreased in aged rats treated with ABH. With the addition of ABH, erectile responses improved in the aged rats (P < .05). Oral inhibition of arginase with ABH results in improved erectile function in aged rats, resulting in erectile hemodynamics similar to young rats. This represents the first documentation of systemic arginase inhibition positively affecting corporal cavernosal function.