Faculty Collaboration Database

Diabetic-induced endothelial dysfunction in rat aorta: role of hydroxyl radicals. Cardiovasc Res 1997 Apr;34(1):145-56

Date

04/01/1997

Pubmed ID

9217884

DOI

10.1016/s0008-6363(96)00237-4

Scopus ID

2-s2.0-0030900360 (requires institutional sign-in at Scopus site)   168 Citations

Abstract

OBJECTIVE: Previous studies suggest a role of superoxide anion radicals (.O2-) in impaired endothelium-dependent relaxation of diabetic blood vessels; however, the role of secondary reactive oxygen species remains unclear. In the present study, we investigated a role of various potential reactive oxygen species in diabetic endothelial dysfunction.

METHODS: Thoracic aortic rings from 8-week streptozotocin-induced diabetic and age-matched control rats were mounted in isolated tissue baths. Endothelium-dependent relaxation to acetylcholine (ACH) and endothelium-independent relaxation to nitroglycerin (NTG) were assessed in precontracted rings.

RESULTS: ACH-induced relaxation was impaired in diabetic compared to control rings and was not improved with either indomethacin or daltroban. ACH-induced relaxation in both control and diabetic rings was completely blocked with the nitric oxide synthase inhibitors, L-nitroarginine methyl ester or L-nitroarginine (L-NA). NTG-induced relaxation was insensitive to L-NA and was unaltered by diabetes. Pretreatment with superoxide dismutase (SOD) at activities which did not alter contractile tone failed to alter response to ACH in diabetic rings. Similar results were obtained using either catalase or mannitol. In contrast, the combination of SOD plus catalase or DETAPAC, an inhibitor of metal-facilitated hydroxyl radical (.OH) formation, markedly enhanced relaxation to ACH in diabetic but not in control rings. Neither the combination of SOD plus catalase nor DETAPAC altered the sensitivity or relaxation to NTG in control rings with or without endothelium. In diabetic rings with endothelium, both DETAPAC or SOD plus catalase increased sensitivity but not maximum relaxation to NTG. In diabetic rings without endothelium, relaxation and sensitivity to NTG were unaltered by either treatment. In L-NA-treated diabetic rings with endothelium, sensitivity and relaxation to NTG was unaltered by either DETAPAC or SOD plus catalase.

CONCLUSION: Diabetic endothelium produces increases in both .O2- and H2O2 leading to enhanced intracellular production of .OH. Thus, .OH are implicated in diabetes-induced endothelial dysfunction.

Author List

Pieper GM, Langenstroer P, Siebeneich W

Author

Peter Langenstroer MD Professor in the Urologic Surgery department at Medical College of Wisconsin

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

Acetylcholine
Animals
Aorta, Thoracic
Catalase
Cyclooxygenase Inhibitors
Diabetes Mellitus, Experimental
Diuretics, Osmotic
Dose-Response Relationship, Drug
Endothelium, Vascular
Hydroxyl Radical
In Vitro Techniques
Indomethacin
Male
Mannitol
NG-Nitroarginine Methyl Ester
Nitric Oxide Synthase
Nitroarginine
Nitroglycerin
Norepinephrine
Phenylacetates
Rats
Rats, Sprague-Dawley
Receptors, Thromboxane
Sulfonamides
Superoxide Dismutase
Vasoconstrictor Agents
Vasodilator Agents