Faculty Collaboration Database

Chronic treatment in vivo with dimethylthiourea, a hydroxyl radical scavenger, prevents diabetes-induced endothelial dysfunction. J Cardiovasc Pharmacol 1996 Dec;28(6):741-5

Date

12/01/1996

Pubmed ID

8961070

DOI

10.1097/00005344-199612000-00002

Scopus ID

2-s2.0-0029798152 (requires institutional sign-in at Scopus site)   49 Citations

Abstract

Oxidative stress is believed to play a role in diabetes-induced vascular complications. In this study, we tested whether chronic treatment with a known hydroxyl radical scavenger, dimethylthiourea (DMTU), could prevent endothelial dysfunction in diabetes. Lewis strain rats were made diabetic by an intravenous injection of streptozotocin. A subgroup of diabetic animals received daily intraperitoneal injections of 50 mg/kg DMTU beginning at 72 h after streptozotocin and throughout 8 weeks of diabetes. Diabetes caused an increase in aortic catalase activity (an index of compensatory in vivo oxidative stress) that was not prevented by long-term DMTU treatment. Long-term treatment of diabetic animals with DMTU did not alter serum insulin levels, blood glucose concentrations, or total glycosylated hemoglobin. Descending thoracic aortas were isolated, sectioned into rings and suspended in isolated tissue baths, and contracted with a submaximal concentration of norepinephrine. Relaxation to the endothelium-dependent vasodilator, acetylcholine, was impaired in diabetic aortas, whereas relaxation to A23187 and nitroglycerin was unaltered. DMTU treatment prevented the diabetes-induced impairment in endothelium-dependent relaxation to acetylcholine but had no effect on relaxations induced by either A23187 or nitroglycerin. These data suggest that chronic exposure to increased levels of hydroxyl radicals in vivo likely play a significant role in the origin of diabetes-associated endothelial dysfunction.

Author List

Pieper GM, Siebeneich W, Roza AM, Jordan M, Adams MB

MESH terms used to index this publication - Major topics in bold

Acetylcholine
Animals
Aorta
Blood Glucose
Calcimycin
Catalase
Diabetes Mellitus, Experimental
Endothelium, Vascular
Free Radical Scavengers
In Vitro Techniques
Insulin
Male
Nitroglycerin
Rats
Thiourea