Diabetes, Vol 42, Issue 2 221-232, Copyright © 1993 by American Diabetes Association

ARTICLES

Prevention of diabetic vascular dysfunction by guanidines. Inhibition of nitric oxide synthase versus advanced glycation end-product formation

RG Tilton, K Chang, KS Hasan, SR Smith, JM Petrash, TP Misko, WM Moore, MG Currie, JA Corbett, ML McDaniel and al. et
Department of Ophthalmology, Washington University School of Medicine, St. Louis, MO 63110.

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.
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				S. G. Shaw, J. P. Boden, E. Biecker, J. Reichen, and B. Rothen Endothelin Antagonism Prevents Diabetic Retinopathy in NOD Mice: A Potential Role of the Angiogenic Factor Adrenomedullin. Experimental Biology and Medicine, June 1, 2006; 231(6): 1101 - 1105. [Abstract] [Full Text] [PDF]

				M. Lassila, K. K. Seah, T. J. Allen, V. Thallas, M. C. Thomas, R. Candido, W. C. Burns, J. M. Forbes, A. C. Calkin, M. E. Cooper, et al. Accelerated Nephropathy in Diabetic Apolipoprotein E-Knockout Mouse: Role of Advanced Glycation End Products J. Am. Soc. Nephrol., August 1, 2004; 15(8): 2125 - 2138. [Abstract] [Full Text] [PDF]

				A. J. Barber and D. A. Antonetti Mapping the Blood Vessels with Paracellular Permeability in the Retinas of Diabetic Rats Invest. Ophthalmol. Vis. Sci., December 1, 2003; 44(12): 5410 - 5416. [Abstract] [Full Text] [PDF]

				C. A. Gunnett, D. D. Heistad, and F. M. Faraci Gene-Targeted Mice Reveal a Critical Role for Inducible Nitric Oxide Synthase in Vascular Dysfunction During Diabetes Stroke, December 1, 2003; 34(12): 2970 - 2974. [Abstract] [Full Text] [PDF]

				T. Wendt, N. Tanji, J. Guo, B. I. Hudson, A. Bierhaus, R. Ramasamy, B. Arnold, P. P. Nawroth, S. F. Yan, V. D'Agati, et al. Glucose, Glycation, and RAGE: Implications for Amplification of Cellular Dysfunction in Diabetic Nephropathy J. Am. Soc. Nephrol., May 1, 2003; 14(5): 1383 - 1395. [Abstract] [Full Text] [PDF]

				R. A. Kowluru Effect of Reinstitution of Good Glycemic Control on Retinal Oxidative Stress and Nitrative Stress in Diabetic Rats Diabetes, March 1, 2003; 52(3): 818 - 823. [Abstract] [Full Text] [PDF]

				J. M. Forbes, M. E. Cooper, V. Thallas, W. C. Burns, M. C. Thomas, G. C. Brammar, F. Lee, S. L. Grant, L. A. Burrell, G. Jerums, et al. Reduction of the Accumulation of Advanced Glycation End Products by ACE Inhibition in Experimental Diabetic Nephropathy Diabetes, November 1, 2002; 51(11): 3274 - 3282. [Abstract] [Full Text] [PDF]

				J. L. Wilkinson-Berka, D. J. Kelly, S. M. Koerner, K. Jaworski, B. Davis, V. Thallas, and M. E. Cooper ALT-946 and Aminoguanidine, Inhibitors of Advanced Glycation, Improve Severe Nephropathy in the Diabetic Transgenic (mREN-2)27 Rat Diabetes, November 1, 2002; 51(11): 3283 - 3289. [Abstract] [Full Text] [PDF]

				R. A. Kowluru and P. Koppolu Termination of Experimental Galactosemia in Rats, and Progression of Retinal Metabolic Abnormalities Invest. Ophthalmol. Vis. Sci., October 1, 2002; 43(10): 3287 - 3291. [Abstract] [Full Text] [PDF]

				H. Naggar, M. S. Ola, P. Moore, W. Huang, C. C. Bridges, V. Ganapathy, and S. B. Smith Downregulation of Reduced-Folate Transporter by Glucose in Cultured RPE Cells and in RPE of Diabetic Mice Invest. Ophthalmol. Vis. Sci., February 1, 2002; 43(2): 556 - 563. [Abstract] [Full Text] [PDF]

				C. C. Bridges, M. S. Ola, P. D. Prasad, A. El-Sherbeny, V. Ganapathy, and S. B. Smith Regulation of taurine transporter expression by NO in cultured human retinal pigment epithelial cells Am J Physiol Cell Physiol, December 1, 2001; 281(6): C1825 - C1836. [Abstract] [Full Text] [PDF]

				D. J. KELLY, R. E. GILBERT, A. J. COX, T. SOULIS, G. JERUMS, and M. E. COOPER Aminoguanidine Ameliorates Overexpression of Prosclerotic Growth Factors and Collagen Deposition in Experimental Diabetic Nephropathy J. Am. Soc. Nephrol., October 1, 2001; 12(10): 2098 - 2107. [Abstract] [Full Text] [PDF]

				R. A. Kowluru, J. Tang, and T. S. Kern Abnormalities of Retinal Metabolism in Diabetes and Experimental Galactosemia: VII. Effect of Long-Term Administration of Antioxidants on the Development of Retinopathy Diabetes, August 1, 2001; 50(8): 1938 - 1942. [Abstract] [Full Text] [PDF]

				T. S. Kern and R. L. Engerman Pharmacological Inhibition of Diabetic Retinopathy: Aminoguanidine and Aspirin Diabetes, July 1, 2001; 50(7): 1636 - 1642. [Abstract] [Full Text] [PDF]

				Q. Xu, T. Qaum, and A. P. Adamis Sensitive Blood-Retinal Barrier Breakdown Quantitation Using Evans Blue Invest. Ophthalmol. Vis. Sci., March 1, 2001; 42(3): 789 - 794. [Abstract] [Full Text]

				T. S. Kern, J. Tang, M. Mizutani, R. A. Kowluru, R. H. Nagaraj, G. Romeo, F. Podesta, and M. Lorenzi Response of Capillary Cell Death to Aminoguanidine Predicts the Development of Retinopathy: Comparison of Diabetes and Galactosemia Invest. Ophthalmol. Vis. Sci., November 1, 2000; 41(12): 3972 - 3978. [Abstract] [Full Text]

				R. Komers, J. N. Lindsley, T. T. Oyama, K. M. Allison, and S. Anderson Role of neuronal nitric oxide synthase (NOS1) in the pathogenesis of renal hemodynamic changes in diabetes Am J Physiol Renal Physiol, September 1, 2000; 279(3): F573 - F583. [Abstract] [Full Text] [PDF]

				T. J. Lyons, W. Li, B. Wojciechowski, M. C. Wells–Knecht, K. J. Wells–Knecht, and A. J. Jenkins Aminoguanidine and the Effects of Modified LDL on Cultured Retinal Capillary Cells Invest. Ophthalmol. Vis. Sci., April 1, 2000; 41(5): 1176 - 1180. [Abstract] [Full Text]

				H. G. Seo, T. Nishinaka, and C. Yabe-Nishimura Nitric Oxide Up-Regulates Aldose Reductase Expression in Rat Vascular Smooth Muscle Cells: A Potential Role for Aldose Reductase in Vascular Remodeling Mol. Pharmacol., April 1, 2000; 57(4): 709 - 717. [Abstract] [Full Text]

				L.-O. Hattenbach, A. Allers, C. Klais, F. Koch, and M. Hecker L-Arginine-Nitric Oxide Pathway-Related Metabolites in the Aqueous Humor of Diabetic Patients Invest. Ophthalmol. Vis. Sci., January 1, 2000; 41(1): 213 - 217. [Abstract] [Full Text]

				R. VEELKEN, K. F. HILGERS, A. HARTNER, A. HAAS, K. P. BÖHMER, and R. B. STERZEL Nitric Oxide Synthase Isoforms and Glomerular Hyperfiltration in Early Diabetic Nephropathy J. Am. Soc. Nephrol., January 1, 2000; 11(1): 71 - 79. [Abstract] [Full Text]

				K. Miyamoto, S. Khosrof, S.-E. Bursell, R. Rohan, T. Murata, A. C. Clermont, L. P. Aiello, Y. Ogura, and A. P. Adamis Prevention of leukostasis and vascular leakage in streptozotocin-induced diabetic retinopathy via intercellular adhesion molecule-1 inhibition PNAS, September 14, 1999; 96(19): 10836 - 10841. [Abstract] [Full Text] [PDF]

				H. Takano, S. Manchikalapudi, X.-L. Tang, Y. Qiu, A. Rizvi, A. K. Jadoon, Q. Zhang, and R. Bolli Nitric Oxide Synthase Is the Mediator of Late Preconditioning Against Myocardial Infarction in Conscious Rabbits Circulation, August 4, 1998; 98(5): 441 - 449. [Abstract] [Full Text] [PDF]

				W. G. Mayhan and K. P. Patel Treatment with dimethylthiourea prevents impaired dilatation of the basilar artery during diabetes mellitus Am J Physiol Heart Circ Physiol, June 1, 1998; 274(6): H1895 - H1901. [Abstract] [Full Text] [PDF]

				G. M. Pieper Review of Alterations in Endothelial Nitric Oxide Production in Diabetes : Protective Role of Arginine on Endothelial Dysfunction Hypertension, May 1, 1998; 31(5): 1047 - 1060. [Full Text] [PDF]

				B. Corman, M. Duriez, P. Poitevin, D. Heudes, P. Bruneval, A. Tedgui, and B. I. Levy Aminoguanidine prevents age-related arterial stiffening and cardiac hypertrophy PNAS, February 3, 1998; 95(3): 1301 - 1306. [Abstract] [Full Text] [PDF]

				N. K. Worrall, K. Chang, W. S. Lejeune, T. P. Misko, P. M. Sullivan, T. B. Ferguson Jr., and J. R. Williamson TNF-alpha causes reversible in vivo systemic vascular barrier dysfunction via NO-dependent and -independent mechanisms Am J Physiol Heart Circ Physiol, December 1, 1997; 273(6): H2565 - H2574. [Abstract] [Full Text] [PDF]

				Y. Horie, R. Wolf, and D. N. Granger Role of nitric oxide in gut ischemia-reperfusion-induced hepatic microvascular dysfunction Am J Physiol Gastrointest Liver Physiol, November 1, 1997; 273(5): G1007 - G1013. [Abstract] [Full Text] [PDF]

				S. Ishiyama, M. Hiroe, T. Nishikawa, S. Abe, T. Shimojo, H. Ito, S. Ozasa, K. Yamakawa, M. Matsuzaki, M. U. Mohammed, et al. Nitric Oxide Contributes to the Progression of Myocardial Damage in Experimental Autoimmune Myocarditis in Rats Circulation, January 21, 1997; 95(2): 489 - 496. [Abstract] [Full Text]

				Y. Tajiri, C. Moller, and V. Grill Long Term Effects of Aminoguanidine on Insulin Release and Biosynthesis: Evidence That the Formation of Advanced Glycosylation End Products Inhibits B Cell Function Endocrinology, January 1, 1997; 138(1): 273 - 280. [Abstract] [Full Text] [PDF]

				N. K. Worrall, K. Chang, G. M. Suau, W. S. Allison, T. P. Misko, P. M. Sullivan, R. G. Tilton, J. R. Williamson, and T. B. Ferguson Jr Inhibition of Inducible Nitric Oxide Synthase Prevents Myocardial and Systemic Vascular Barrier Dysfunction During Early Cardiac Allograft Rejection Circ. Res., May 1, 1996; 78(5): 769 - 779. [Abstract] [Full Text]

				C. G. Sobey, R. M. Brooks II, and D. D. Heistad Evidence That Expression of Inducible Nitric Oxide Synthase in Response to Endotoxin Is Augmented in Atherosclerotic Rabbits Circ. Res., September 1, 1995; 77(3): 536 - 543. [Abstract] [Full Text]