title: Impact of rosiglitazone and glyburide on nitrosative stress and myocardial blood flow regulation in type 2 diabetes mellitus.
abstract: Cardiovascular disease, the leading cause of death in patients with type 2 diabetes mellitus (T2DM), is usually preceded by endothelial dysfunction and altered myocardial blood flow (MBF) regulation. Hyperglycemia, oxidative-nitrosative stress, systemic inflammation, and insulin resistance are implicated in the pathogenesis of abnormal MBF regulation, myocardial ischemia, and apoptosis. However, the impact of oral antihyperglycemic therapy on myocardial perfusion is controversial. Our objective was to explore the effect of rosiglitazone and glyburide on nitrosative stress and MBF regulation in subjects with T2DM. [(13)N]ammonia positron emission tomography and cold pressor testing were used in 27 diabetic subjects (mean age, 49 +/- 11 years; glycohemoglobin, 7% +/- 1.5%) randomized to either rosiglitazone 8 mg/d or glyburide 10 mg/d for 6 months. Isotope dilution gas chromatography-mass spectrometry was used to quantify plasma 3-nitrotyrosine, a stable marker of reactive nitrogen species. At 6 months, there were no significant differences between groups in the mean glycohemoglobin, blood pressure, or plasma lipids. Rosiglitazone significantly reduced plasma nitrotyrosine, high-sensitivity C-reactive protein, and von Willebrand antigen (P < .03 for all) and significantly increased plasma adiponectin (P < .05). No significant changes in these parameters were observed with glyburide. Treatment with glyburide, but not rosiglitazone, resulted in a significant deterioration in both resting and stress MBF. Rosiglitazone, but not glyburide, ameliorated markers of nitrosative stress and inflammation in subjects with T2DM without impairing myocardial perfusion.
authors.affiliation: Department of Internal Medicine, Division of Metabolism, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Rodica
authors.initials: R
authors.lastname: Pop-Busui
authors.forename: Elif
authors.initials: E
authors.lastname: Oral
authors.forename: David
authors.initials: D
authors.lastname: Raffel
authors.forename: Jaeman
authors.initials: J
authors.lastname: Byun
authors.forename: Valida
authors.initials: V
authors.lastname: Bajirovic
authors.forename: Anuradha
authors.initials: A
authors.lastname: Vivekanandan-Giri
authors.forename: Aaron
authors.initials: A
authors.lastname: Kellogg
authors.forename: Subramaniam
authors.initials: S
authors.lastname: Pennathur
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Stevens
mesh_terms: D052242:Adiponectin / Q000378:metabolism; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D015331:Cohort Studies; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D005260:Female; D005905:Glyburide / Q000009:adverse effects / Q000627:therapeutic use*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism; D049268:Positron-Emission Tomography; D026361:Reactive Nitrogen Species / Q000097:blood*; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000009:adverse effects / Q000627:therapeutic use*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000097:blood; D014841:von Willebrand Factor / Q000276:immunology / Q000378:metabolism
chemical_list: D052242:Adiponectin; D001786:Blood Glucose; D002097:C-Reactive Protein; D005905:Glyburide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D026361:Reactive Nitrogen Species; D000077154:Rosiglitazone; D045162:Thiazolidinediones; D014443:Tyrosine; D014841:von Willebrand Factor; C499918:ADIPOQ protein, human; C029417:Von Willebrand antigen; C002744:3-nitrotyrosine