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

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.