J Korean Diabetes Assoc.  2002 Feb;26(1):46-56.

Mechanism of Impaired Endothelium-dependent Vasodilation in Otsuka Long-Evans Tokushima Fatty (OLETF) Rats

• Chun KJ
• Son SM
• Kim IJ
• Kim CD
• Yoo SD
• Kim YK

Abstract

BACKGROUND: Impaired vascular endothelium-dependent relaxation and augmented contractile responses have been reported in several long-term animals hyperglycemia models and human diabetic patients. Since oxidative stress has been implicated as a contributor to impaired vascular function, the mechanism of an impaired endothelium-dependent vasodilation in Otsuka Long-Evans Tokushima Fatty (OLETF) rats was investigated.
METHODS
This present study was undertaken to characterize both the vascular production and the enzymatic source of the superoxide anion in the type 2 diabetic rats.
RESULTS
In the thoracic aortas of OLETF rats, endothelium-dependent relaxation was markedly attenuated compared to that of the control rats (LETO, Long-Evans Tokushima Otsuka) in association with a significant increase in superoxide production (2421.39+/-07.01 nmol/min/mg). There was no difference in eNOS expression between the OLETF rats and LETO rats. The increased production of superoxide anion was significantly attenuated by diphenyleneiodonium (DPI, 10 mol/L), NAD (P)H oxidase inhibitor. In line with these results, studies using various enzyme inhibitors such as DPI, allopurinol, rotenone and L-NMMA suggest that the main source of superoxide anions in the aorta is NAD (P)H oxidase.
CONCLUSION
These results suggest that enhanced NAD(P)H oxidase activity and reduced nitric oxide (NO) availability through an interaction between NO and superoxide anion contribute to the impaired endothelium-dependent vasodilation in OLETF rats.

Keyword

NAD(P)H oxidase; Relaxation; Superoxide anion; eNOS; OLETF rat

MeSH Terms

Allopurinol
Animals
Aorta
Aorta, Thoracic
Enzyme Inhibitors
Humans
Hyperglycemia
NAD
NADPH Oxidase
Nitric Oxide
omega-N-Methylarginine
Oxidative Stress
Oxidoreductases
Rats*
Rats, Inbred OLETF
Relaxation
Rotenone
Superoxides
Vasodilation*
Allopurinol
Enzyme Inhibitors
NAD
NADPH Oxidase
Nitric Oxide
Oxidoreductases
Rotenone
Superoxides
omega-N-Methylarginine