Arginase II deletion increases corpora cavernosa relaxation in diabetic mice

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Introduction. Diabetes-induced erectile dysfunction involves elevated arginase (Arg) activity and expression. Because nitric oxide (NO) synthase and Arg share and compete for their substrate L-arginine, NO production is likely linked to regulation of Arg. Arg is highly expressed and implicated in erectile dysfunction. Aim. It was hypothesized that Arg-II isoform deletion enhances relaxation function of corpora cavernosal (CC) smooth muscle in a streptozotocin (STZ) diabetic model. Methods. Eight weeks after STZ-induced diabetes, vascular functional studies, Arg activity assay, and protein expression levels of Arg and constitutive NOS (using Western blots) were assessed in CC tissues from nondiabetic wild type (WT), diabetic (D) WT (WT+D), Arg-II knockout (KO), and Arg-II KO+D mice (N=8-10 per group). Main Outcome Measures. Inhibition or lack of arginase results in facilitation of CC relaxation in diabetic CC. Results. Strips of CC from Arg-II KO mice exhibited an enhanced maximum endothelium-dependent relaxation (from 70+3% to 84+4%) and increased nitrergic relaxation (by 55%, 71%, 42%, 42%, and 24% for 1, 2, 4, 8 and 16Hz, respectively) compared with WT mice. WT+D mice showed a significant reduction of endothelium-dependent maximum relaxation (44+8%), but this impairment of relaxation was significantly prevented in Arg-II KO+D mice (69+4%). Sympathetic-mediated and alpha-adrenergic agent-induced contractile responses also were increased in CC strips from D compared with non-D controls. Contractile responses were significantly lower in Arg-II KO control and D versus the WT groups. WT+D mice increased Arg activity (1.5-fold) and Arg-II protein expression and decreased total and phospho-eNOS at Ser-1177, and nNOS levels. These alterations were not seen in Arg-II KO mice. Additionally, the Arg inhibitor BEC (50μM) enhanced nitrergic and endothelium-dependent relaxation in CC of WT+D mice. Conclusion. These studies show for the first time that Arg-II deletion improves CC relaxation in type 1 diabetes.

Original languageEnglish (US)
Pages (from-to)722-733
Number of pages12
JournalJournal of Sexual Medicine
Volume8
Issue number3
DOIs
StatePublished - Jan 1 2011

Fingerprint

Arginase
Knockout Mice
Endothelium
Erectile Dysfunction
Experimental Diabetes Mellitus

Keywords

  • Arginase
  • Diabetes
  • Erectile Dysfunction
  • Nitric Oxide

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology
  • Urology

Cite this

Arginase II deletion increases corpora cavernosa relaxation in diabetic mice. / Flores Toque, Haroldo Alfredo; Tostes, Rita C.; Yao, Lin; Xu, Zhimin; Webb, R Clinton; Caldwell, Ruth B; Caldwell, Robert William.

In: Journal of Sexual Medicine, Vol. 8, No. 3, 01.01.2011, p. 722-733.

Research output: Contribution to journalArticle

@article{8b875deaf4d5476db795fa40c641b4f3,
title = "Arginase II deletion increases corpora cavernosa relaxation in diabetic mice",
abstract = "Introduction. Diabetes-induced erectile dysfunction involves elevated arginase (Arg) activity and expression. Because nitric oxide (NO) synthase and Arg share and compete for their substrate L-arginine, NO production is likely linked to regulation of Arg. Arg is highly expressed and implicated in erectile dysfunction. Aim. It was hypothesized that Arg-II isoform deletion enhances relaxation function of corpora cavernosal (CC) smooth muscle in a streptozotocin (STZ) diabetic model. Methods. Eight weeks after STZ-induced diabetes, vascular functional studies, Arg activity assay, and protein expression levels of Arg and constitutive NOS (using Western blots) were assessed in CC tissues from nondiabetic wild type (WT), diabetic (D) WT (WT+D), Arg-II knockout (KO), and Arg-II KO+D mice (N=8-10 per group). Main Outcome Measures. Inhibition or lack of arginase results in facilitation of CC relaxation in diabetic CC. Results. Strips of CC from Arg-II KO mice exhibited an enhanced maximum endothelium-dependent relaxation (from 70+3{\%} to 84+4{\%}) and increased nitrergic relaxation (by 55{\%}, 71{\%}, 42{\%}, 42{\%}, and 24{\%} for 1, 2, 4, 8 and 16Hz, respectively) compared with WT mice. WT+D mice showed a significant reduction of endothelium-dependent maximum relaxation (44+8{\%}), but this impairment of relaxation was significantly prevented in Arg-II KO+D mice (69+4{\%}). Sympathetic-mediated and alpha-adrenergic agent-induced contractile responses also were increased in CC strips from D compared with non-D controls. Contractile responses were significantly lower in Arg-II KO control and D versus the WT groups. WT+D mice increased Arg activity (1.5-fold) and Arg-II protein expression and decreased total and phospho-eNOS at Ser-1177, and nNOS levels. These alterations were not seen in Arg-II KO mice. Additionally, the Arg inhibitor BEC (50μM) enhanced nitrergic and endothelium-dependent relaxation in CC of WT+D mice. Conclusion. These studies show for the first time that Arg-II deletion improves CC relaxation in type 1 diabetes.",
keywords = "Arginase, Diabetes, Erectile Dysfunction, Nitric Oxide",
author = "{Flores Toque}, {Haroldo Alfredo} and Tostes, {Rita C.} and Lin Yao and Zhimin Xu and Webb, {R Clinton} and Caldwell, {Ruth B} and Caldwell, {Robert William}",
year = "2011",
month = "1",
day = "1",
doi = "10.1111/j.1743-6109.2010.02098.x",
language = "English (US)",
volume = "8",
pages = "722--733",
journal = "Journal of Sexual Medicine",
issn = "1743-6095",
publisher = "Wiley-Blackwell",
number = "3",

}

TY - JOUR

T1 - Arginase II deletion increases corpora cavernosa relaxation in diabetic mice

AU - Flores Toque, Haroldo Alfredo

AU - Tostes, Rita C.

AU - Yao, Lin

AU - Xu, Zhimin

AU - Webb, R Clinton

AU - Caldwell, Ruth B

AU - Caldwell, Robert William

PY - 2011/1/1

Y1 - 2011/1/1

N2 - Introduction. Diabetes-induced erectile dysfunction involves elevated arginase (Arg) activity and expression. Because nitric oxide (NO) synthase and Arg share and compete for their substrate L-arginine, NO production is likely linked to regulation of Arg. Arg is highly expressed and implicated in erectile dysfunction. Aim. It was hypothesized that Arg-II isoform deletion enhances relaxation function of corpora cavernosal (CC) smooth muscle in a streptozotocin (STZ) diabetic model. Methods. Eight weeks after STZ-induced diabetes, vascular functional studies, Arg activity assay, and protein expression levels of Arg and constitutive NOS (using Western blots) were assessed in CC tissues from nondiabetic wild type (WT), diabetic (D) WT (WT+D), Arg-II knockout (KO), and Arg-II KO+D mice (N=8-10 per group). Main Outcome Measures. Inhibition or lack of arginase results in facilitation of CC relaxation in diabetic CC. Results. Strips of CC from Arg-II KO mice exhibited an enhanced maximum endothelium-dependent relaxation (from 70+3% to 84+4%) and increased nitrergic relaxation (by 55%, 71%, 42%, 42%, and 24% for 1, 2, 4, 8 and 16Hz, respectively) compared with WT mice. WT+D mice showed a significant reduction of endothelium-dependent maximum relaxation (44+8%), but this impairment of relaxation was significantly prevented in Arg-II KO+D mice (69+4%). Sympathetic-mediated and alpha-adrenergic agent-induced contractile responses also were increased in CC strips from D compared with non-D controls. Contractile responses were significantly lower in Arg-II KO control and D versus the WT groups. WT+D mice increased Arg activity (1.5-fold) and Arg-II protein expression and decreased total and phospho-eNOS at Ser-1177, and nNOS levels. These alterations were not seen in Arg-II KO mice. Additionally, the Arg inhibitor BEC (50μM) enhanced nitrergic and endothelium-dependent relaxation in CC of WT+D mice. Conclusion. These studies show for the first time that Arg-II deletion improves CC relaxation in type 1 diabetes.

AB - Introduction. Diabetes-induced erectile dysfunction involves elevated arginase (Arg) activity and expression. Because nitric oxide (NO) synthase and Arg share and compete for their substrate L-arginine, NO production is likely linked to regulation of Arg. Arg is highly expressed and implicated in erectile dysfunction. Aim. It was hypothesized that Arg-II isoform deletion enhances relaxation function of corpora cavernosal (CC) smooth muscle in a streptozotocin (STZ) diabetic model. Methods. Eight weeks after STZ-induced diabetes, vascular functional studies, Arg activity assay, and protein expression levels of Arg and constitutive NOS (using Western blots) were assessed in CC tissues from nondiabetic wild type (WT), diabetic (D) WT (WT+D), Arg-II knockout (KO), and Arg-II KO+D mice (N=8-10 per group). Main Outcome Measures. Inhibition or lack of arginase results in facilitation of CC relaxation in diabetic CC. Results. Strips of CC from Arg-II KO mice exhibited an enhanced maximum endothelium-dependent relaxation (from 70+3% to 84+4%) and increased nitrergic relaxation (by 55%, 71%, 42%, 42%, and 24% for 1, 2, 4, 8 and 16Hz, respectively) compared with WT mice. WT+D mice showed a significant reduction of endothelium-dependent maximum relaxation (44+8%), but this impairment of relaxation was significantly prevented in Arg-II KO+D mice (69+4%). Sympathetic-mediated and alpha-adrenergic agent-induced contractile responses also were increased in CC strips from D compared with non-D controls. Contractile responses were significantly lower in Arg-II KO control and D versus the WT groups. WT+D mice increased Arg activity (1.5-fold) and Arg-II protein expression and decreased total and phospho-eNOS at Ser-1177, and nNOS levels. These alterations were not seen in Arg-II KO mice. Additionally, the Arg inhibitor BEC (50μM) enhanced nitrergic and endothelium-dependent relaxation in CC of WT+D mice. Conclusion. These studies show for the first time that Arg-II deletion improves CC relaxation in type 1 diabetes.

KW - Arginase

KW - Diabetes

KW - Erectile Dysfunction

KW - Nitric Oxide

UR - http://www.scopus.com/inward/record.url?scp=79951976114&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79951976114&partnerID=8YFLogxK

U2 - 10.1111/j.1743-6109.2010.02098.x

DO - 10.1111/j.1743-6109.2010.02098.x

M3 - Article

C2 - 21054801

AN - SCOPUS:79951976114

VL - 8

SP - 722

EP - 733

JO - Journal of Sexual Medicine

JF - Journal of Sexual Medicine

SN - 1743-6095

IS - 3

ER -