Effects of chelator treatment on aorta and corpus cavernosum from diabetic rats

A Keegan, M A Cotter, Norman E Cameron

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Transition-metal catalyzed reactions contribute to oxidative stress, which has been implicated in the pathogenesis of diabetic complications. The aim was to evaluate the effects of treatment with the transition metal chelator trientine on endothelium-dependent relaxation of aorta and corpus cavernosum from streptozotocin-induced diabetes of 8 weeks duration in rats. Effects on cavernosum autonomic innervation were also examined. Diabetes caused a 30.1 +/- 3.8% reduction in maximum aorta endothelium-dependent relaxation to acetylcholine (ACh), which was markedly attenuated (72.7 +/- 10.6%) by trientine treatment. Reversal treatment (4 weeks untreated diabetes, 4 weeks trientine) did not effect endothelium-dependent relaxation compared with aortas from rats with 4 weeks of diabetes, however, there was a 22.5 +/- 6.2% improvement compared with 8 weeks of diabetes. Eight weeks of diabetes caused a 41.5 +/- 6.6% reduction in corpus cavernosum endothelium-dependent maximum relaxation to ACh that was 70.1 +/- 16.9% prevented by trientine. Cavernosum nonadrenergic, noncholinergic (NANC) nerve stimulation caused frequency-dependent relaxation to a maximum of 40.9 +/- 2.4%, which was reduced by diabetes to 24.2 +/- 2.1%. Trientine partially prevented this deficit, maximum relaxation being 31.9 +/- 2.3%. Thus, metal chelator treatment has beneficial effects on aorta and cavernosum endothelium-dependent relaxation and on cavernosum NANC innervation. (C) 1999 Elsevier Science Inc.

Original languageEnglish
Pages (from-to)536-543
Number of pages8
JournalFree Radical Biology and Medicine
Volume27
Publication statusPublished - 1999

Keywords

  • diabetes mellitus
  • endothelium
  • nitric oxide
  • oxidative stress
  • impotence
  • NANC
  • neuropathy
  • free radicals
  • ENDOTHELIUM-DEPENDENT RELAXATION
  • ALDOSE REDUCTASE INHIBITION
  • NITRIC-OXIDE SYNTHASE
  • SMOOTH-MUSCLE
  • FREE-RADICALS
  • L-ARGININE
  • SUPEROXIDE-DISMUTASE
  • CYCLIC-GMP
  • DYSFUNCTION
  • CONTRACTION

Cite this

Effects of chelator treatment on aorta and corpus cavernosum from diabetic rats. / Keegan, A ; Cotter, M A ; Cameron, Norman E.

In: Free Radical Biology and Medicine, Vol. 27, 1999, p. 536-543.

Research output: Contribution to journalArticle

Keegan, A ; Cotter, M A ; Cameron, Norman E. / Effects of chelator treatment on aorta and corpus cavernosum from diabetic rats. In: Free Radical Biology and Medicine. 1999 ; Vol. 27. pp. 536-543.
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abstract = "Transition-metal catalyzed reactions contribute to oxidative stress, which has been implicated in the pathogenesis of diabetic complications. The aim was to evaluate the effects of treatment with the transition metal chelator trientine on endothelium-dependent relaxation of aorta and corpus cavernosum from streptozotocin-induced diabetes of 8 weeks duration in rats. Effects on cavernosum autonomic innervation were also examined. Diabetes caused a 30.1 +/- 3.8{\%} reduction in maximum aorta endothelium-dependent relaxation to acetylcholine (ACh), which was markedly attenuated (72.7 +/- 10.6{\%}) by trientine treatment. Reversal treatment (4 weeks untreated diabetes, 4 weeks trientine) did not effect endothelium-dependent relaxation compared with aortas from rats with 4 weeks of diabetes, however, there was a 22.5 +/- 6.2{\%} improvement compared with 8 weeks of diabetes. Eight weeks of diabetes caused a 41.5 +/- 6.6{\%} reduction in corpus cavernosum endothelium-dependent maximum relaxation to ACh that was 70.1 +/- 16.9{\%} prevented by trientine. Cavernosum nonadrenergic, noncholinergic (NANC) nerve stimulation caused frequency-dependent relaxation to a maximum of 40.9 +/- 2.4{\%}, which was reduced by diabetes to 24.2 +/- 2.1{\%}. Trientine partially prevented this deficit, maximum relaxation being 31.9 +/- 2.3{\%}. Thus, metal chelator treatment has beneficial effects on aorta and cavernosum endothelium-dependent relaxation and on cavernosum NANC innervation. (C) 1999 Elsevier Science Inc.",
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AU - Cotter, M A

AU - Cameron, Norman E

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N2 - Transition-metal catalyzed reactions contribute to oxidative stress, which has been implicated in the pathogenesis of diabetic complications. The aim was to evaluate the effects of treatment with the transition metal chelator trientine on endothelium-dependent relaxation of aorta and corpus cavernosum from streptozotocin-induced diabetes of 8 weeks duration in rats. Effects on cavernosum autonomic innervation were also examined. Diabetes caused a 30.1 +/- 3.8% reduction in maximum aorta endothelium-dependent relaxation to acetylcholine (ACh), which was markedly attenuated (72.7 +/- 10.6%) by trientine treatment. Reversal treatment (4 weeks untreated diabetes, 4 weeks trientine) did not effect endothelium-dependent relaxation compared with aortas from rats with 4 weeks of diabetes, however, there was a 22.5 +/- 6.2% improvement compared with 8 weeks of diabetes. Eight weeks of diabetes caused a 41.5 +/- 6.6% reduction in corpus cavernosum endothelium-dependent maximum relaxation to ACh that was 70.1 +/- 16.9% prevented by trientine. Cavernosum nonadrenergic, noncholinergic (NANC) nerve stimulation caused frequency-dependent relaxation to a maximum of 40.9 +/- 2.4%, which was reduced by diabetes to 24.2 +/- 2.1%. Trientine partially prevented this deficit, maximum relaxation being 31.9 +/- 2.3%. Thus, metal chelator treatment has beneficial effects on aorta and cavernosum endothelium-dependent relaxation and on cavernosum NANC innervation. (C) 1999 Elsevier Science Inc.

AB - Transition-metal catalyzed reactions contribute to oxidative stress, which has been implicated in the pathogenesis of diabetic complications. The aim was to evaluate the effects of treatment with the transition metal chelator trientine on endothelium-dependent relaxation of aorta and corpus cavernosum from streptozotocin-induced diabetes of 8 weeks duration in rats. Effects on cavernosum autonomic innervation were also examined. Diabetes caused a 30.1 +/- 3.8% reduction in maximum aorta endothelium-dependent relaxation to acetylcholine (ACh), which was markedly attenuated (72.7 +/- 10.6%) by trientine treatment. Reversal treatment (4 weeks untreated diabetes, 4 weeks trientine) did not effect endothelium-dependent relaxation compared with aortas from rats with 4 weeks of diabetes, however, there was a 22.5 +/- 6.2% improvement compared with 8 weeks of diabetes. Eight weeks of diabetes caused a 41.5 +/- 6.6% reduction in corpus cavernosum endothelium-dependent maximum relaxation to ACh that was 70.1 +/- 16.9% prevented by trientine. Cavernosum nonadrenergic, noncholinergic (NANC) nerve stimulation caused frequency-dependent relaxation to a maximum of 40.9 +/- 2.4%, which was reduced by diabetes to 24.2 +/- 2.1%. Trientine partially prevented this deficit, maximum relaxation being 31.9 +/- 2.3%. Thus, metal chelator treatment has beneficial effects on aorta and cavernosum endothelium-dependent relaxation and on cavernosum NANC innervation. (C) 1999 Elsevier Science Inc.

KW - diabetes mellitus

KW - endothelium

KW - nitric oxide

KW - oxidative stress

KW - impotence

KW - NANC

KW - neuropathy

KW - free radicals

KW - ENDOTHELIUM-DEPENDENT RELAXATION

KW - ALDOSE REDUCTASE INHIBITION

KW - NITRIC-OXIDE SYNTHASE

KW - SMOOTH-MUSCLE

KW - FREE-RADICALS

KW - L-ARGININE

KW - SUPEROXIDE-DISMUTASE

KW - CYCLIC-GMP

KW - DYSFUNCTION

KW - CONTRACTION

M3 - Article

VL - 27

SP - 536

EP - 543

JO - Free Radical Biology and Medicine

JF - Free Radical Biology and Medicine

SN - 0891-5849

ER -