PT  - JOURNAL ARTICLE
AU  - Tilton, Ronald G
AU  - Chang, Katherine
AU  - Hasan, Khalid S
AU  - Smith, Samuel R
AU  - Petrash, J Mark
AU  - Misko, Thomas P
AU  - Moore, William M
AU  - Currie, Mark G
AU  - Corbett, John A
AU  - McDaniel, Michael L
AU  - Williamson, Joseph R
TI  - Prevention of Diabetic Vascular Dysfunction by Guanidines: Inhibition of Nitric Oxide Synthase Versus Advanced Glycation End-Product Formation
AID  - 10.2337/diab.42.2.221
DP  - 1993 Feb 01
TA  - Diabetes
PG  - 221--232
VI  - 42
IP  - 2
4099  - http://diabetes.diabetesjournals.org/content/42/2/221.short
4100  - http://diabetes.diabetesjournals.org/content/42/2/221.full
SO  - Diabetes1993 Feb 01; 42
AB  - This study was undertaken to compare the ability of two guanidine compounds (aminoguanidine and methylguanidine), with different in vitro effects on NO synthase activity and AGE formation, to inhibit diabetic vascular dysfunction developing early after the onset of diabetes. In rats with STZ-induced diabetes of 5-wk duration, regional vascular [125I]albumin permeation was increased about two- to threefold in ocular tissues, sciatic nerve, and aorta; in general, both guanidine compounds normalized albumin permeation in diabetic rats without affecting it in controls. Methylguanidine was only ∼7% as effective as aminoguanidine as an inhibitor of AGE formation from L-lysine and G6P; both compounds were poor inhibitors of AR. Methylguanidine was ∼1–5% as potent as aminoguanidine and L-NMMA as an inhibitor of the cytokine- and endotoxin-inducible isoform of NO synthase. In contrast, the potency of methylguanidine as an inhibitor of the constitutive isoform of NO synthase was comparable to that of aminoguanidine, and both guanidine compounds were much less effective than L-NMMA. These observations suggest a role for a relative or absolute increase in NO production in the pathogenesis of early diabetic vascular dysfunction and raise the possibility that inhibition of diabetic vascular functional changes by aminoguanidine may reflect inhibition of NO synthase activity rather than, or in addition to, prevention of AGE formation.