Abstract
We examined the responses of basilar arteries taken from Otsuka Long-Evans Tokushima
Fatty (OLETF) rats, a type 2 diabetes model. Both the nitric oxide (NO)-mediated relaxation
and the cyclic 3′,5′-guanosine monophosphate (cGMP) production elicited by acetylcholine
(ACh) were much weaker in OLETF rats than in age-matched control Long Evans Tokushima
Otsuka (LETO) rats. The contraction induced by an NO synthase (NOS) inhibitor [NG-nitro-l-arginine (l-NNA)] was weaker in the OLETF group. In that group, application of apocynin, an NAD(P)H
oxidase inhibitor, normalized (i) ACh-induced relaxation, (ii) l-NNA-induced contraction, and (iii) ACh-induced cGMP production to the LETO levels.
Superoxide anion production was greater in basilar arteries from OLETF rats than in
those from LETO rats. The protein expression of gp91phox, an NAD(P)H oxidase subunit, was upregulated in the OLETF arteries (versus LETO ones).
These results suggest that the existence of endothelial dysfunction in basilar arteries
in type 2 diabetes is related to increased oxidative stress mediated via NAD(P)H oxidase.
Possibly, an impairment of NO-dependent relaxation responses and a basal impairment
of NO signaling may be responsible for the increased risk of adverse cerebrovascular
events in type 2 diabetes.
Keywords
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Article info
Publication history
Published online: July 11, 2006
Accepted:
June 2,
2006
Received in revised form:
April 13,
2006
Received:
August 29,
2005
Identification
Copyright
© 2006 Published by Elsevier Inc.
