Chronic oral administration of the arginase inhibitor 2(S)-amino-6-boronohexanoic acid (ABH) improves erectile function in aged rats

J Androl. Nov-Dec 2012;33(6):1169-75. doi: 10.2164/jandrol.111.015834. Epub 2012 Apr 5.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Aging / physiology
  • Aminocaproates / administration & dosage
  • Aminocaproates / therapeutic use*
  • Animals
  • Arginase
  • Boron Compounds / administration & dosage
  • Boron Compounds / therapeutic use*
  • Electric Stimulation
  • Enzyme Inhibitors / administration & dosage
  • Enzyme Inhibitors / therapeutic use*
  • Erectile Dysfunction / drug therapy*
  • Male
  • Penile Erection / physiology*
  • Penis / enzymology
  • Penis / innervation
  • Rats
  • Rats, Inbred F344

Substances

  • 2-amino-6-boronohexanoic acid
  • Aminocaproates
  • Boron Compounds
  • Enzyme Inhibitors
  • Arginase