Interaction between advanced glycation end products formation and vascular responses in femoral and coronary arteries from exercised diabetic rats

• Published in: PloS one Vol. 7; no. 12; p. e53318
• Main Authors: Delbin, Maria A, Davel, Ana Paula C, Couto, Gisele Kruger, de Araújo, Gustavo G, Rossoni, Luciana Venturini, Antunes, Edson, Zanesco, Angelina
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 28-12-2012; Public Library of Science (PLoS)
• Subjects: Acetylcholine; Advanced glycosylation end products; Age; Animal tissues; Animals; Antioxidants; Antioxidants (Nutrients); Antioxidants - metabolism; Antioxidants - pharmacology; Arteries; Bioavailability; Biology; Biomarkers; Biophysics; Carboxymethyllysine; Cardiovascular disease; Catalase; Copper; Coronary artery; Coronary vessels; Coronary Vessels - drug effects; Coronary Vessels - metabolism; Coronary Vessels - physiopathology; Diabetes; Diabetes mellitus; Diabetes Mellitus, Experimental - chemically induced; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Experimental - physiopathology; Diabetes Mellitus, Experimental - therapy; Dose-Response Relationship, Drug; Endothelium; Endothelium, Vascular - drug effects; Endothelium, Vascular - physiopathology; Endothelium-Dependent Relaxing Factors - metabolism; Endothelium-Dependent Relaxing Factors - pharmacology; Exercise; Femoral Artery - drug effects; Femoral Artery - metabolism; Femoral Artery - physiopathology; Femur; Fitness training programs; Food; Glycation End Products, Advanced - metabolism; Glycation End Products, Advanced - pharmacology; Glycosylation; Hyperglycemia; Insulin; Lysine; Male; Manganese; Medicine; Nitric oxide; Nitrogen oxides; Oxygen; Phenylephrine; Physical Conditioning, Animal; Physical education; Physical fitness; Physiology; Protein expression; Proteins; Pulmonary arteries; Rats; Rats, Wistar; Reactive oxygen species; Reactive Oxygen Species - metabolism; Reactive Oxygen Species - pharmacology; Rodents; Shear stress; Single-nucleotide polymorphism; Smooth muscle; Sodium; Sodium nitroprusside; Streptozocin; Studies; Superoxide dismutase; Superoxides; Thiobarbituric acid; Type 2 diabetes; Vasodilation; Vasodilator agents; Zinc
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0053318

The majority of studies have investigated the effect of exercise training (TR) on vascular responses in diabetic animals (DB), but none evaluated nitric oxide (NO) and advanced glycation end products (AGEs) formation associated with oxidant and antioxidant activities in femoral and coronary arteries from trained diabetic rats. Our hypothesis was that 8-week TR would alter AGEs levels in type 1 diabetic rats ameliorating vascular responsiveness.
Male Wistar rats were divided into control sedentary (C/SD), sedentary diabetic (SD/DB), and trained diabetic (TR/DB). DB was induced by streptozotocin (i.p.: 60 mg/kg). TR was performed for 60 min per day, 5 days/week, during 8 weeks. Concentration-response curves to acetylcholine (ACh), sodium nitroprusside (SNP), phenylephrine (PHE) and tromboxane analog (U46619) were obtained. The protein expressions of eNOS, receptor for AGEs (RAGE), Cu/Zn-SOD and Mn-SOD were analyzed. Tissues NO production and reactive oxygen species (ROS) generation were evaluated. Plasma nitrate/nitrite (NO(x)⁻), superoxide dismutase (SOD), catalase (CAT), thiobarbituric acid reactive substances (TBARS) and N(ε)-(carboxymethyl) lysine (CML, AGE biomarker). A rightward shift in the concentration-response curves to ACh was observed in femoral and coronary arteries from SD/DB that was accompanied by an increase in TBARS and CML levels. Decreased in the eNOS expression, tissues NO production and NO(x)⁻ levels were associated with increased ROS generation. A positive interaction between the beneficial effect of TR on the relaxing responses to ACh and the reduction in TBARS and CML levels were observed without changing in antioxidant activities. The eNOS protein expression, tissues NO production and ROS generation were fully re-established in TR/DB, but plasma NO(x)⁻ levels were partially restored.
Shear stress induced by TR fully restores the eNOS/NO pathway in both preparations from non-treated diabetic rats, however, a massive production of AGEs still affecting relaxing responses possibly involving other endothelium-dependent vasodilator agents, mainly in coronary artery.