Faculty Collaboration Database

Evaluation of the mechanism of endothelial dysfunction in the genetically-diabetic BB rat. Life Sci 1996;58(9):PL147-52

Date

01/01/1996

Pubmed ID

8632717

DOI

10.1016/0024-3205(95)02360-7

Scopus ID

2-s2.0-0030058769 (requires institutional sign-in at Scopus site)   59 Citations

Abstract

Endothelial dysfunction is known to occur in chemically-induced animal models of diabetes. The BB diabetic rat is a genetic diabetes-prone model which more closely resembles Type I diabetes mellitus. In this study, we examined the role of superoxide anion radical and cyclooxygenase activity on endothelial dysfunction in aorta of the spontaneous diabetic BB rat. Vascular endothelial function was studied in vitro in aortic rings from 8-wk diabetic rats and age-matched nondiabetic littermates. There was no alteration in reactivity to norepinephrine as a result of diabetes. Relaxation to acetylcholine (but not nitroglycerin) was impaired in diabetic rings. Relaxation to acetylcholine was abolished by 100 microM L-nitroarginine but unaltered by an equimolar concentration of aminoguanidine (an inducible nitric oxide synthase inhibitor) in both control and diabetic rings. Incubation with 10 microM indomethacin did not alter relaxation to acetylcholine in either control or diabetic rings. In contrast, addition of 20 U/ml superoxide dismutase enhanced relaxation to acetylcholine in diabetic rings but had no effect on relaxation to acetylcholine in control rings. Thus, nitric oxide-mediated, endothelium-dependent relaxation is diminished in aortic rings of the genetic diabetic BB rat. Furthermore, superoxide anion radicals but not cyclooxygenase products play an important role in endothelial dysfunction in this genetic diabetic model.

Author List

Pieper GM, Moore-Hilton G, Roza AM

Author

Allan Roza MD Emeritus Professor in the Surgery department at Medical College of Wisconsin

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

Acetylcholine
Animals
Aorta, Thoracic
Arginine
Diabetes Mellitus, Type 1
Endothelium, Vascular
Enzyme Inhibitors
Guanidines
In Vitro Techniques
Indomethacin
Muscle, Smooth, Vascular
Nitric Oxide Synthase
Nitroarginine
Rats
Rats, Inbred BB
Reference Values
Vasodilation