title: Impact of AT2 receptor deficiency on postnatal cardiovascular development.
abstract: BACKGROUND
  The angiotensin II receptor subtype 2 (AT2 receptor) is ubiquitously and highly expressed in early postnatal life. However, its role in postnatal cardiac development remained unclear.
  
  
  RESULTS
  Hearts from 1, 7, 14 and 56 days old wild-type (WT) and AT2 receptor-deficient (KO) mice were extracted for histomorphometrical analysis as well as analysis of cardiac signaling and gene expression. Furthermore, heart and body weights of examined animals were recorded and echocardiographic analysis of cardiac function as well as telemetric blood pressure measurements were performed. Moreover, gene expression, sarcomere shortening and calcium transients were examined in ventricular cardiomyocytes isolated from both genotypes. KO mice exhibited an accelerated body weight gain and a reduced heart to body weight ratio as compared to WT mice in the postnatal period. However, in adult KO mice the heart to body weight ratio was significantly increased most likely due to elevated systemic blood pressure. At postnatal day 7 ventricular capillarization index and the density of α-smooth muscle cell actin-positive blood vessels were higher in KO mice as compared to WT mice but normalized during adolescence. Echocardiographic assessment of cardiac systolic function at postnatal day 7 revealed decreased contractility of KO hearts in response to beta-adrenergic stimulation. Moreover, cardiomyocytes from KO mice showed a decreased sarcomere shortening and an increased peak Ca(2+) transient in response to isoprenaline when stimulated concomitantly with angiotensin II.
  
  
  CONCLUSIONS
  The AT2 receptor affects postnatal cardiac growth possibly via reducing body weight gain and systemic blood pressure. Moreover, it moderately attenuates postnatal vascularization of the heart and modulates the beta adrenergic response of the neonatal heart. These AT2 receptor-mediated effects may be implicated in the physiological maturation process of the heart.
authors.affiliation: Department of Cardiovascular Surgery, University Heart Center, Hamburg, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Biermann
authors.forename: Andreas
authors.initials: A
authors.lastname: Heilmann
authors.forename: Michael
authors.initials: M
authors.lastname: Didié
authors.forename: Saskia
authors.initials: S
authors.lastname: Schlossarek
authors.forename: Azadeh
authors.initials: A
authors.lastname: Wahab
authors.forename: Michael
authors.initials: M
authors.lastname: Grimm
authors.forename: Maria
authors.initials: M
authors.lastname: Römer
authors.forename: Hermann
authors.initials: H
authors.lastname: Reichenspurner
authors.forename: Karim R
authors.initials: KR
authors.lastname: Sultan
authors.forename: Anna
authors.initials: A
authors.lastname: Steenpass
authors.forename: Süleyman
authors.initials: S
authors.lastname: Ergün
authors.forename: Sonia
authors.initials: S
authors.lastname: Donzelli
authors.forename: Lucie
authors.initials: L
authors.lastname: Carrier
authors.forename: Heimo
authors.initials: H
authors.lastname: Ehmke
authors.forename: Wolfram H
authors.initials: WH
authors.lastname: Zimmermann
authors.forename: Lutz
authors.initials: L
authors.lastname: Hein
authors.forename: Rainer H
authors.initials: RH
authors.lastname: Böger
authors.forename: Ralf A
authors.initials: RA
authors.lastname: Benndorf
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D009320:Atrial Natriuretic Factor / Q000235:genetics; D001794:Blood Pressure; D001835:Body Weight; D002118:Calcium / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology; D015870:Gene Expression; D006321:Heart / Q000254:growth & development* / Q000502:physiology*; D015151:Immunoblotting; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D009200:Myocardial Contraction / Q000235:genetics / Q000502:physiology; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics; D044139:Receptor, Angiotensin, Type 2 / Q000172:deficiency* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012518:Sarcomeres / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D013997:Time Factors; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D051028:bcl-2-Associated X Protein / Q000235:genetics
chemical_list: C494827:Bax protein, mouse; D002316:Cardiotonic Agents; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D014662:Vasoconstrictor Agents; D051028:bcl-2-Associated X Protein; D000804:Angiotensin II; D009320:Atrial Natriuretic Factor; D007545:Isoproterenol; D002118:Calcium