title: Left ventricular function in mice lacking the AT2 receptor.
abstract: OBJECTIVE
  The role of the AT2 receptor in the heart is incompletely understood. We investigated left ventricular performance in AT2 receptor knockout mice, with and without deoxycorticosterone acetate (DOCA)-salt treatment. Given the putative opposing functions of the AT1 and AT2 receptor, we also analysed AT1 receptor expression in the left ventricle.
  
  
  METHODS
  We used a miniaturized conductance-manometer system to measure pressure-volume loops for analysing left ventricular performance under baseline conditions and after increasing peripheral vascular resistance. We determined left ventricular AT1-receptor expression by RNase-protection assays.
  
  
  RESULTS
  In AT2 receptor knockout mice, end-systolic and end-diastolic volumes were lower than in wild-type mice, so that pressure-volume loops were shifted leftward. Left ventricular systolic and diastolic kinetics were not different between the groups. AT2 receptor knockout mice and wild-type mice both stabilized their reduced stroke volume after laparatomy as peripheral resistance was increased. DOCA-salt treatment increased elastance in AT2 receptor knockout mice, compared to controls. Furthermore, AT2 receptor knockout mice had a steeper increase in dP/dtmax. Left ventricular AT1 receptor gene expression was increased in AT2 receptor knockout mice and was not down-regulated in response to DOCA-salt treatment. Finally, the hearts of AT2 receptor knockout mice were smaller than controls, but increased in size in response to DOCA-salt treatment.
  
  
  CONCLUSIONS
  AT2 receptor knockout mice displayed no major changes in left ventricular function at baseline or in response to DOCA-salt treatment, compared to wild-type mice. The AT2 receptor may be important to AT1 receptor expression in response to DOCA-salt challenge and may have some influence on cardiac growth responses.
authors.affiliation: Franz Volhard Clinic and Max Delbrück Center for Molecular Medicine, Medical Faculty of the Charité, Humboldt University of Berlin, Germany.
authors.forename: V
authors.initials: V
authors.lastname: Gross
authors.forename: T
authors.initials: T
authors.lastname: Walther
authors.forename: A F
authors.initials: AF
authors.lastname: Milia
authors.forename: K
authors.initials: K
authors.lastname: Walter
authors.forename: W
authors.initials: W
authors.lastname: Schneider
authors.forename: F C
authors.initials: FC
authors.lastname: Luft
mesh_terms: D000818:Animals; D003900:Desoxycorticosterone / Q000494:pharmacology; D006321:Heart / Q000033:anatomy & histology; D008297:Male; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D009206:Myocardium / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D012016:Reference Values; D012965:Sodium Chloride / Q000494:pharmacology; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D003900:Desoxycorticosterone; D012965:Sodium Chloride