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.
|Number of pages||5|
|Journal||European Journal of Pharmacology|
|Publication status||Published - 2004|
- SMOOTH-MUSCLE RELAXATION
- NITRIC-OXIDE SYNTHASE
- HYDROXYL RADICAL SCAVENGER
- ENDOTHELIAL DYSFUNCTION