Effects of the Peroxynitrite decomposition catalyst, FeTMPyP, on function of corpus cavernosum from diabetic mice

Matthew Robert Nangle, Mary Anne Cotter, Norman E Cameron

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Peroxynitrite, the reaction product of nitric oxide and superoxide, may contribute to vascular tissue oxidant stress in diabetes mellitus. The aim was to establish whether the peroxynitrite decomposition catalyst 5,10,15,20-tetrakis(N-methyl-4'-pyridyl)porphyrinato iron III (FeTMPyP) could improve nitric oxide-dependent autonomic nerve and microvascular penile function in the diabetic mouse. Diabetes was induced by streptozotocin; duration was 6 weeks. Intervention FeTMPyP treatment (25 mg kg(-1) day(-1)) was given for 2 weeks following 4 weeks untreated diabetes. Corpus cavernosum were isolated in organ baths for measurement of agonist or electrical stimulation-evoked nerve-mediated tension responses. Maximum nitrergic nerve-mediated relaxation of phenylephrine-precontracted cavernosum was approximately 35% reduced by diabetes; FeTMPyP treatment reversed this deficit by 45%. The concentration response-curve for nitric oxide-mediated endothelium-dependent relaxation to acetylcholine was attenuated by diabetes; FeTMPyP restored the deficit to the nondiabetic range. Sensitivity (EC50) to the nitric oxide donor, sodium nitroprusside, was reduced by approximately 0.56 log(10) M units in diabetes: however, FeTMPyP treatment failed to significantly reverse this deficit. Therefore, the peroxynitrite mechanism contributes to nitric oxide-dependent diabetic autonomic neuropathy and vasculopathy and may be a potential target for clinical trials using peroxynitrite decomposition catalysts. (C) 2004 Elsevier B.V. All rights reserved.

Original languageEnglish
Pages (from-to)143-148
Number of pages5
JournalEuropean Journal of Pharmacology
Volume502
Issue number1-2
DOIs
Publication statusPublished - 2004

Keywords

  • peroxynitrite
  • FeTMPyP
  • diabetes
  • SMOOTH-MUSCLE RELAXATION
  • NITRIC-OXIDE SYNTHASE
  • HYDROXYL RADICAL SCAVENGER
  • ENDOTHELIAL DYSFUNCTION
  • CONDUCTION-VELOCITY
  • BLOOD-FLOW
  • MELLITUS
  • RATS
  • EXPRESSION
  • DIMETHYLTHIOUREA

Cite this

Effects of the Peroxynitrite decomposition catalyst, FeTMPyP, on function of corpus cavernosum from diabetic mice. / Nangle, Matthew Robert; Cotter, Mary Anne; Cameron, Norman E.

In: European Journal of Pharmacology, Vol. 502, No. 1-2, 2004, p. 143-148.

Research output: Contribution to journalArticle

Nangle, Matthew Robert ; Cotter, Mary Anne ; Cameron, Norman E. / Effects of the Peroxynitrite decomposition catalyst, FeTMPyP, on function of corpus cavernosum from diabetic mice. In: European Journal of Pharmacology. 2004 ; Vol. 502, No. 1-2. pp. 143-148.
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AB - Peroxynitrite, the reaction product of nitric oxide and superoxide, may contribute to vascular tissue oxidant stress in diabetes mellitus. The aim was to establish whether the peroxynitrite decomposition catalyst 5,10,15,20-tetrakis(N-methyl-4'-pyridyl)porphyrinato iron III (FeTMPyP) could improve nitric oxide-dependent autonomic nerve and microvascular penile function in the diabetic mouse. Diabetes was induced by streptozotocin; duration was 6 weeks. Intervention FeTMPyP treatment (25 mg kg(-1) day(-1)) was given for 2 weeks following 4 weeks untreated diabetes. Corpus cavernosum were isolated in organ baths for measurement of agonist or electrical stimulation-evoked nerve-mediated tension responses. Maximum nitrergic nerve-mediated relaxation of phenylephrine-precontracted cavernosum was approximately 35% reduced by diabetes; FeTMPyP treatment reversed this deficit by 45%. The concentration response-curve for nitric oxide-mediated endothelium-dependent relaxation to acetylcholine was attenuated by diabetes; FeTMPyP restored the deficit to the nondiabetic range. Sensitivity (EC50) to the nitric oxide donor, sodium nitroprusside, was reduced by approximately 0.56 log(10) M units in diabetes: however, FeTMPyP treatment failed to significantly reverse this deficit. Therefore, the peroxynitrite mechanism contributes to nitric oxide-dependent diabetic autonomic neuropathy and vasculopathy and may be a potential target for clinical trials using peroxynitrite decomposition catalysts. (C) 2004 Elsevier B.V. All rights reserved.

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