title: Exendin-4 directly improves endothelial dysfunction in isolated aortas from obese rats through the cAMP or AMPK-eNOS pathways.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Han
authors.forename: Yerong
authors.initials: Y
authors.lastname: Yu
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Sun
authors.forename: Ben
authors.initials: B
authors.lastname: Wang
mesh_terms: D000263:Adenylate Kinase / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism* / Q000502:physiology; D004353:Drug Evaluation, Preclinical; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D000077270:Exenatide; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism* / Q000502:physiology; D009765:Obesity / Q000150:complications / Q000473:pathology* / Q000503:physiopathology; D009924:Organ Culture Techniques; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014688:Venoms / Q000494:pharmacology*
chemical_list: D007004:Hypoglycemic Agents; D010455:Peptides; D014688:Venoms; D000077270:Exenatide; D000242:Cyclic AMP; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D000263:Adenylate Kinase