Literature DB >> 22492840

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

Robert Segal1, Johanna L Hannan, Xiaopu Liu, Omer Kutlu, Arthur L Burnett, Hunter C Champion, Jae Hyung Kim, Jochen Steppan, Dan E Berkowitz, Trinity J Bivalacqua.   

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.

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Year:  2012        PMID: 22492840      PMCID: PMC4029113          DOI: 10.2164/jandrol.111.015834

Source DB:  PubMed          Journal:  J Androl        ISSN: 0196-3635


  38 in total

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Journal:  FASEB J       Date:  2001-05       Impact factor: 5.191

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

Authors:  T J Bivalacqua; W J Hellstrom; P J Kadowitz; H C Champion
Journal:  Biochem Biophys Res Commun       Date:  2001-05-18       Impact factor: 3.575

3.  Gene transfer of endothelial nitric oxide synthase partially restores nitric oxide synthesis and erectile function in streptozotocin diabetic rats.

Authors:  Trinity J Bivalacqua; Mustafa F Usta; Hunter C Champion; Dave Adams; Dennis B Namara; Asim B Abdel-Mageed; Philip J Kadowitz; Wayne J G Hellstrom
Journal:  J Urol       Date:  2003-05       Impact factor: 7.450

4.  Aging-related expression of inducible nitric oxide synthase and markers of tissue damage in the rat penis.

Authors:  M Ferrini; T R Magee; D Vernet; J Rajfer; N F González-Cadavid
Journal:  Biol Reprod       Date:  2001-03       Impact factor: 4.285

5.  Evaluation and treatment of erectile dysfunction in the aging male: a mini-review.

Authors:  Maarten Albersen; Hazem Orabi; Tom F Lue
Journal:  Gerontology       Date:  2011-09-07       Impact factor: 5.140

6.  Decreased trabecular smooth muscle and caveolin-1 expression in the penile tissue of aged rats.

Authors:  M E Bakircioglu; K D Sievert; L Nunes; A Lau; C S Lin; T F Lue
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7.  IL-4 and IL-13 upregulate arginase I expression by cAMP and JAK/STAT6 pathways in vascular smooth muscle cells.

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8.  Evaluation of nitric oxide synthase and arginase in the induction of a Peyronie's-like condition in the rat.

Authors:  T J Bivalacqua; H C Champion; S Leungwattanakij; D Y Yang; J S Hyun; A B Abdel-Mageed; S C Sikka; P J Kadowitz; W J Hellstrom
Journal:  J Androl       Date:  2001 May-Jun

9.  Arginase expression and modulation of IL-1beta-induced nitric oxide generation in rat and human islets of Langerhans.

Authors:  P Stickings; S K Mistry; J-L Boucher; S M Morris; J M Cunningham
Journal:  Nitric Oxide       Date:  2002-12       Impact factor: 4.427

10.  Arginase and autoimmune inflammation in the central nervous system.

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  7 in total

Review 1.  Arginase: an old enzyme with new tricks.

Authors:  Ruth B Caldwell; Haroldo A Toque; S Priya Narayanan; R William Caldwell
Journal:  Trends Pharmacol Sci       Date:  2015-04-27       Impact factor: 14.819

Review 2.  Pharmacokinetics and Pharmacodynamics of Promising Arginase Inhibitors.

Authors:  Khaled S Abdelkawy; Kelsey Lack; Fawzy Elbarbry
Journal:  Eur J Drug Metab Pharmacokinet       Date:  2017-06       Impact factor: 2.441

3.  Influence of arginase polymorphisms and arginase levels/activity on the response to erectile dysfunction therapy with sildenafil.

Authors:  R Lacchini; J J Muniz; Y T D A Nobre; A J Cologna; A C P Martins; J E Tanus-Santos
Journal:  Pharmacogenomics J       Date:  2017-04-04       Impact factor: 3.550

4.  Deregulation of arginase induces bone complications in high-fat/high-sucrose diet diabetic mouse model.

Authors:  Anil Bhatta; Rajnikumar Sangani; Ravindra Kolhe; Haroldo A Toque; Michael Cain; Abby Wong; Nicole Howie; Rahul Shinde; Mohammed Elsalanty; Lin Yao; Norman Chutkan; Monty Hunter; Ruth B Caldwell; Carlos Isales; R William Caldwell; Sadanand Fulzele
Journal:  Mol Cell Endocrinol       Date:  2015-12-17       Impact factor: 4.102

Review 5.  Arginase: A Multifaceted Enzyme Important in Health and Disease.

Authors:  R William Caldwell; Paulo C Rodriguez; Haroldo A Toque; S Priya Narayanan; Ruth B Caldwell
Journal:  Physiol Rev       Date:  2018-04-01       Impact factor: 37.312

Review 6.  Gas what: NO is not the only answer to sexual function.

Authors:  G Yetik-Anacak; R Sorrentino; A E Linder; N Murat
Journal:  Br J Pharmacol       Date:  2014-07-02       Impact factor: 8.739

7.  Cinnamide Derivatives as Mammalian Arginase Inhibitors: Synthesis, Biological Evaluation and Molecular Docking.

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Journal:  Int J Mol Sci       Date:  2016-09-29       Impact factor: 5.923

  7 in total

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