title: Prolonged AMP-activated protein kinase induction impairs vascular functions.
abstract: AMP-activated protein kinase (AMPK) is a regulator of cellular metabolism and is involved in the pathogenesis of several diseases, including type 2 diabetes and cardiovascular diseases. Data showing the effects of AMPK on vasculature are controversial. Therefore, the aim of this study was to determine the impact of prolonged AMPK activation on vascular functions. For this purpose we have examined the role of AMPK in endothelium-dependent and -independent relaxation and vascular contractions. For this, we incubated thoracic aortic rings, from rats, with AMPK activator 5-aminoimidazole-4-carboxamide-1-4-ribofuranoside (AICAR, 500 μmol/L or 2 mmol/L) in the presence or absence of AMPK inhibitor compound C (10 μmol/L). Next, cumulative dose-response curves to acetylcholine (ACh) (10(-9)-10(-4) mol/L), nitroglycerine (NG) (10(-9)-3 × 10(-5) mol/L), and noradrenaline (NA) (10(-9)-10(-4) mol/L) were obtained. Endothelial nitric oxide synthase (eNOS) protein expression was determined. Our results show that endothelium-dependent relaxation was inhibited after AICAR treatment, and that this effect was reversed by AMPK inhibition. Moreover, AICAR enhanced the contractile response to NA and caused a decrease in eNOS protein expression. In conclusion, prolonged AMPK induction causes endothelial impairment, possibly via increased degradation and (or) reduced expression of eNOS.
authors.affiliation: Ege University, Faculty of Pharmacy, Department of Pharmacology, Bornova-Izmir 35100, Turkey.
authors.forename: Saadet
authors.initials: S
authors.lastname: Turkseven
authors.forename: Elif
authors.initials: E
authors.lastname: Ertuna
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism / Q000502:physiology*; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000502:physiology*; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000502:physiology*; D014664:Vasodilation / Q000502:physiology*
chemical_list: D052250:Nitric Oxide Synthase Type III; D055372:AMP-Activated Protein Kinases