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Arginase II Deletion Improves Diabetes‐Induced Neurogenic and Endothelial Dysfunction in Mice Corpora Cavernosa
Author(s) -
Toque Haroldo Alfredo Flores,
Xu Zhimin,
Tostes Rita C.,
Webb R. Clinton,
Caldwell Ruth B.,
Caldwell R. William
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.lb514
Subject(s) - endocrinology , medicine , enos , arginase , chemistry , knockout mouse , acetylcholine , stimulation , diabetes mellitus , streptozotocin , nitric oxide , contraction (grammar) , arginine , nitric oxide synthase , biochemistry , receptor , amino acid
Diabetes‐induced erectile dysfunction involves elevated arginase (AG) activity. Because NO synthase and AG share and compete for their substrate L‐arginine, NO production is likely linked to regulation of AG. We hypothesized that AG II isoform deletion enhances corpora cavernosal (CC) smooth muscle relaxation in a streptozotocin diabetic (D) model using wild type (WT) and AG II knockout (KO) mice. AG activity and expression and functional response of CC were assessed. CC strips from AG II KO mice exhibited enhanced relaxation to both nitrergic stimulation (1–32 Hz) and the endothelium‐dependent (ED) acetylcholine (84±4%) compared to WT mice (70±3%). WT+D mice showed a significant reduction of nitrergic and ED maximum relaxation (44±8%), but this impairment was prevented in AG II KO+D mice (69±4%). Alpha‐adrenergic agent‐induced contractile responses were increased in CC from WT+D compared to non D controls. Contractile responses were significantly decreased in AG II KO control and D mice vs the WT groups. Diabetes in WT mice increased AG activity and expression (II) and decreased nNOS and phospho‐eNOS levels. AG II KO mice did not exhibit these changes. Additionally, the AG inhibitor BEC (50 μM) enhanced nitrergic and ED relaxation in CC of WT+D mice. Thus, we show for the first time that AG II deletion prevents D‐impairment in CC relaxation. Our findings indicate that AG II plays a role in impaired erectile function.