Prevention of diabetic vascular dysfunction by guanidines. Inhibition of nitric oxide synthase versus advanced glycation end-product formation. Diabetes 1993 Feb;42(2):221-32
Date
02/01/1993Pubmed ID
7678825DOI
10.2337/diab.42.2.221Scopus ID
2-s2.0-0027400644 (requires institutional sign-in at Scopus site) 320 CitationsAbstract
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 approximately 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 approximately 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.
Author List
Tilton RG, Chang K, Hasan KS, Smith SR, Petrash JM, Misko TP, Moore WM, Currie MG, Corbett JA, McDaniel MLAuthor
John A. Corbett PhD Chair, Professor in the Biochemistry department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Aldehyde ReductaseAmino Acid Oxidoreductases
Animals
Arginine
Benzothiazoles
Blood Pressure
Body Weight
Capillary Permeability
Citrulline
Diabetes Mellitus, Experimental
Diabetic Angiopathies
Glycation End Products, Advanced
Guanidines
Imidazoles
Imidazolidines
Inositol
Iodine Radioisotopes
Male
Methylguanidine
Naphthalenes
Nitric Oxide Synthase
Phthalazines
Rats
Rats, Sprague-Dawley
Retina
Sciatic Nerve
Serum Albumin, Bovine
Sorbitol
Thiazoles
Uvea
omega-N-Methylarginine
