title: Cardiac hypertrophy and fibrosis in chronic L-NAME-treated AT2 receptor-deficient mice.
abstract: BACKGROUND
  The role of angiotensin II type 1 (AT1) and type 2 (AT2) receptors in cardiac hypertrophy and fibrosis is incompletely understood. The availability of AT2 receptor-deficient mice (AT2 -/y) makes it possible to study the effects of AT1 receptors without the confounding influence of AT2 receptor activity.
  
  
  OBJECTIVE
  To test the hypothesis that the AT2 receptor affords protection from left ventricular hypertrophy and fibrosis in chronic hypertension induced by N-nitro-L-arginine methyl ester (L-NAME).
  
  
  METHODS
  Four groups of mice were studied over a period of 3 weeks: AT2 -/y mice with and without L-NAME, and AT2 +/y mice with and without L-NAME.
  
  
  METHODS
  Blood pressure and heart rate were monitored by telemetry in groups of AT2 +/y and AT2 -/y mice for 4 weeks. L-NAME groups received the compound in drinking water for the last 3 weeks. We determined left ventricular AT1 receptor expression, cardiac hypertrophy and fibrosis, with and without L-NAME treatment. We used a miniaturized conductance-manometer system to measure pressure-volume loops at the time when the animals were killed.
  
  
  RESULTS
  AT2 -/y mice treated with L-NAME showed worse left ventricular hypertrophy, more perivascular fibrosis and greater concentrations of brain natriuretic peptide than did AT2 +/y mice treated with L-NAME. The end-systolic pressure-volume relationship, an index of left ventricular contractility, was decreased in AT2 -/y mice treated with L-NAME.
  
  
  CONCLUSIONS
  The AT2 receptor is not essential for development of L-NAME-induced cardiac hypertrophy, fibrosis and concomitant changes in left ventricular performance. In contrast, the AT2 receptor offers a protective effect.
authors.affiliation: Max-Delbrück-Center for Molecular Medicine, Berlin, Germany.
authors.forename: Volkmar
authors.initials: V
authors.lastname: Gross
authors.forename: Michael
authors.initials: M
authors.lastname: Obst
authors.forename: Eva
authors.initials: E
authors.lastname: Kiss
authors.forename: Jürgen
authors.initials: J
authors.lastname: Janke
authors.forename: Istvan
authors.initials: I
authors.lastname: Mazak
authors.forename: Erdenechimeg
authors.initials: E
authors.lastname: Shagdarsuren
authors.forename: Dominik N
authors.initials: DN
authors.lastname: Müller
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Langenickel
authors.forename: Hermann-Josef
authors.initials: HJ
authors.lastname: Gröne
authors.forename: Friedrich C
authors.initials: FC
authors.lastname: Luft
mesh_terms: D000818:Animals; D001794:Blood Pressure; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005355:Fibrosis; D006339:Heart Rate; D006973:Hypertension / Q000150:complications / Q000503:physiopathology*; D017379:Hypertrophy, Left Ventricular / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics* / Q000378:metabolism; D016277:Ventricular Function, Left
chemical_list: D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D019331:NG-Nitroarginine Methyl Ester