Prevention of Diabetic Vascular Dysfunction by Guanidines: Inhibition of Nitric Oxide Synthase Versus Advanced Glycation End-Product Formation

• DOI: 10.2337/diab.42.2.221
• Publication Date: 2013-09-19T17:22:06Z
• Authors: Ronald G Tilton; Katherine Chang; Khalid S Hasan; Samuel R Smith; J Mark Petrash; Thomas P Misko; William M Moore; Mark G Currie; John A Corbett; Michael L McDaniel; Joseph R Williamson
• Keywords: Advanced glycation end-product

This study was undertaken to compare the ability of two guanidine compounds (aminoguanidine and methylguanidine), with different in vitro effects on NO synthase activity AGE formation, inhibit diabetic vascular dysfunction developing early after onset diabetes. In rats STZ-induced diabetes 5-wk duration, regional [125I]albumin permeation increased about two- threefold ocular tissues, sciatic nerve, aorta; general, both normalized albumin without affecting it controls. Methylguanidine only ∼7% as effective aminoguanidine an inhibitor formation from L-lysine G6P; were poor inhibitors AR. ∼1–5% potent L-NMMA cytokine- endotoxin-inducible isoform synthase. contrast, potency methylguanidine constitutive comparable that aminoguanidine, much less than L-NMMA. These observations suggest a role for relative or absolute increase production pathogenesis raise possibility inhibition functional changes by may reflect rather than, addition to, prevention formation.