Exendin-4 directly improves endothelial dysfunction in isolated aortas from obese rats through the cAMP or AMPK-eNOS pathways.

Abstract:

AIMS:To determine whether exendin-4 might directly improve endothelial dysfunction in aorta isolated from high-fat diet-induced obese rats. METHODS:Wistar rats were randomly divided into control and obesity (OB) groups and fed. Vascular segments of obese rats were incubated in organ bath in the presence or absence of exendin-4. Nitric oxide (NO) production and nuclear transcription factor kappa B expression in vascular rings were measured. The aortic rings of the obese rats were then incubated in an organ bath with exendin-4 in the presence or absence of the following inhibitors: the AMPK, the adenylate cyclase and the NO synthase inhibitor. RESULTS:The maximum endothelium-dependent vasodilatation (EDV) value was severely reduced in the OB group. Exendin-4 treatment significantly increased the NO level, improved endothelium-dependent vasodilatation and reduced expression of NF-κB in the obese group. The beneficial effect of exendin-4 on EDV in obese rats was partly attenuated in the presence of the specific inhibitors. CONCLUSION:Exendin-4 directly improves impaired EDV of aortae from obese rats. The beneficial effect of exendin-4 appears to be mediated in part via stimulation of cAMP/AMPK-related signalling pathways and enhancement of endothelial nitric oxide synthase activity.

authors

Han L,Yu Y,Sun X,Wang B

doi

10.1016/j.diabres.2012.04.001

subject

Has Abstract

pub_date

2012-09-01 00:00:00

pages

453-60

issue

3

eissn

0168-8227

issn

1872-8227

pii

S0168-8227(12)00133-7

journal_volume

97

pub_type

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