title: The inhibitory effect of leptin on angiotensin II-induced vasoconstriction is blunted in spontaneously hypertensive rats.
abstract: OBJECTIVE
  Leptin attenuates the angiotensin II-induced increase of cytosolic calcium ([Ca2+]i) and vasoconstriction in the aorta of normotensive Wistar rats. To determine whether these effects may be altered in hypertension, we assessed the effect of leptin on angiotensin II-induced vascular response in the aorta of 10-week-old spontaneously hypertensive rats (SHR).
  
  
  METHODS
  Contractile responses to angiotensin II (100 nmol/l) in the presence of different concentrations of leptin (0.1, 1, 10, 100 nmol/l) were evaluated in isolated aortic rings by the organ bath system. [Ca2+]i was measured in vascular smooth muscle cells (VSMCs) using Fura-2 fluorescence. The expression of the short (OB-Ra) and long (OB-Rb) isoforms of the leptin receptor in VSMCs was evaluated by real-time reverse transcriptase-polymerase chain reaction and western-blot analysis.
  
  
  RESULTS
  Circulating leptin concentrations were increased in SHR. Serum metabolic parameters, including glucose, insulin, total cholesterol and triglyceride levels, were also elevated in SHR. Leptin did not modify the angiotensin II-induced vasoconstriction in SHR either in intact or endothelium-denuded aortic rings. In addition, leptin was not able either to diminish the angiotensin II-induced the peak rise of [Ca2+]i or to accelerate the recovery rate to basal calcium levels in VSMCs from SHR. However, OB-Ra and OB-Rb mRNA and protein expression were increased in SHR VSMCs.
  
  
  CONCLUSIONS
  The lack of effect of leptin on angiotensin II-induced contraction in the aorta of SHR is due to an impaired handling of [Ca2+]i in VSMCs. Hyperleptinemia and overexpression of OB-R in VSMCs could be compensatory mechanisms against VSMC leptin resistance in genetically hypertensive rats.
authors.affiliation: Metabolic Research Laboratory, Clínica Universitaria de Navarra, Pamplona, Spain.
authors.forename: Amaia
authors.initials: A
authors.lastname: Rodríguez
authors.forename: Gema
authors.initials: G
authors.lastname: Frühbeck
authors.forename: Javier
authors.initials: J
authors.lastname: Gómez-Ambrosi
authors.forename: Victoria
authors.initials: V
authors.lastname: Catalán
authors.forename: Neira
authors.initials: N
authors.lastname: Sáinz
authors.forename: Javier
authors.initials: J
authors.lastname: Díez
authors.forename: Guillermo
authors.initials: G
authors.lastname: Zalba
authors.forename: Ana
authors.initials: A
authors.lastname: Fortuño
mesh_terms: D000704:Analysis of Variance; D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology; D020738:Leptin / Q000008:administration & dosage / Q000378:metabolism*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000098:blood supply*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D020033:Protein Isoforms / Q000096:biosynthesis / Q000187:drug effects; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000187:drug effects; D054411:Receptors, Leptin; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D015415:Biomarkers; D020738:Leptin; D020033:Protein Isoforms; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D000804:Angiotensin II; D002118:Calcium