title: AKT participates in endothelial dysfunction in hypertension.
abstract: BACKGROUND
  In hypertension, reduced nitric oxide production and blunted endothelial vasorelaxation are observed. It was recently reported that AKT phosphorylates and activates endothelial nitric oxide synthase and that impaired kinase activity may be involved in endothelial dysfunction.
  
  
  RESULTS
  To identify the physiological role of the kinase in normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR), we used adenoviral vectors to transfer the human AKT1 gene selectively to the common carotid endothelium. In vitro, endothelial vasorelaxations to acetylcholine, isoproterenol, and insulin were blunted in control carotids from SHR compared with WKY rats, and human AKT1 overexpression corrected these responses. Similarly, blood flow assessed in vivo by Doppler ultrasound was reduced in SHR compared with WKY carotids and normalized after AKT1 gene transfer. In primary cultured endothelial cells, we evaluated AKT phosphorylation, activity, and compartmentalization and observed a mislocalization of the kinase in SHR.
  
  
  CONCLUSIONS
  We conclude that AKT participates in the settings of endothelial dysfunction in SHR rats by impaired membrane localization. Our data suggest that AKT is involved in endothelium dysfunction in hypertension.
authors.affiliation: Department of Clinical Medicine, University of Naples Federico II, Italy. guiaccar@unina.it
authors.forename: Guido
authors.initials: G
authors.lastname: Iaccarino
authors.forename: Michele
authors.initials: M
authors.lastname: Ciccarelli
authors.forename: Daniela
authors.initials: D
authors.lastname: Sorriento
authors.forename: Ersilia
authors.initials: E
authors.lastname: Cipolletta
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Cerullo
authors.forename: Gianni Luigi
authors.initials: GL
authors.lastname: Iovino
authors.forename: Alessandro
authors.initials: A
authors.lastname: Paudice
authors.forename: Andrea
authors.initials: A
authors.lastname: Elia
authors.forename: Gaetano
authors.initials: G
authors.lastname: Santulli
authors.forename: Alfonso
authors.initials: A
authors.lastname: Campanile
authors.forename: Oreste
authors.initials: O
authors.lastname: Arcucci
authors.forename: Lucio
authors.initials: L
authors.lastname: Pastore
authors.forename: Francesco
authors.initials: F
authors.lastname: Salvatore
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Condorelli
authors.forename: Bruno
authors.initials: B
authors.lastname: Trimarco
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001011:Aorta; D017536:Carotid Artery, Common / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology; D002462:Cell Membrane / Q000201:enzymology; D002478:Cells, Cultured / Q000201:enzymology; D042783:Endothelial Cells / Q000201:enzymology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D006973:Hypertension / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology*; D007269:Injections, Intra-Arterial; D007328:Insulin / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D021381:Protein Transport; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011993:Recombinant Fusion Proteins / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014463:Ultrasonography; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D007328:Insulin; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D014665:Vasodilator Agents; D009569:Nitric Oxide; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; C494918:AKT1 protein, human; C494920:Akt1 protein, rat; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D007545:Isoproterenol; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester