title: Expression of bradykinin receptors in the left ventricles of rats with pressure overload hypertrophy and heart failure.
abstract: OBJECTIVE
  Bradykinin exerts cardioprotective effects through bradykinin type-2 receptors (BK-2Rs). After acute myocardial infarction in rat, the heart adapts by increasing its number of BK-2Rs. However, in human chronic end-stage heart failure, the number of BK-2Rs is significantly decreased. Thus, the presence of a cardioprotective BK-2R signaling system may be critical in the prevention of pressure overload-induced heart failure.
  
  
  METHODS
  To explain differences in myocardial BK-2R expression during cardiac overload, we studied: (1). spontaneously hypertensive rats (SHRs) of different ages, and (2). normotensive Sprague-Dawley rats subjected to aortic banding or angiotensin II infusion.
  
  
  RESULTS
  The mRNA levels of BK-2Rs were found to be significantly (P < 0.05) increased in the aging (12 and 20-month-old) SHRs (2.9- and 3-fold, respectively). Similarly, in the Sprague-Dawley rats, the expression of BK-2Rs was increased at 12 h (1.8-fold, P < 0.05) and at 3 days (3.1-fold, P < 0.05) after aortic banding, and at 2 weeks (2.2-fold) after angiotensin II infusion. In the 12-month-old SHRs, with compensated left ventricular hypertrophy (no fibrosis or left ventricular dysfunction), the amount of BK-2Rs was also significantly increased (1.8-fold, P < 0.05). However, in the 20-month-old SHRs, with a dramatic increase in fibrosis and development of diastolic dysfunction and heart failure, the amount of BK-2Rs were significantly decreased (63%, P < 0.05) specifically in the cardiac endothelial cells.
  
  
  CONCLUSIONS
  The present results show that, during pressure overload and compensated left ventricular hypertrophy, the expression of BK-2Rs is increased. However, ongoing pressure overload leads to a loss of BK-2Rs with a dramatic increase in left ventricular fibrosis followed by diastolic dysfunction and heart failure.
authors.affiliation: Wihuri Research Institute, Helsinki, Finland.
authors.forename: Antti
authors.initials: A
authors.lastname: Kuoppala
authors.forename: Naotaka
authors.initials: N
authors.lastname: Shiota
authors.forename: Ken A
authors.initials: KA
authors.lastname: Lindstedt
authors.forename: Jaana
authors.initials: J
authors.lastname: Rysä
authors.forename: Hanna K
authors.initials: HK
authors.lastname: Leskinen
authors.forename: Marja
authors.initials: M
authors.lastname: Luodonpää
authors.forename: Inka
authors.initials: I
authors.lastname: Liesmaa
authors.forename: Heikki
authors.initials: H
authors.lastname: Ruskoaho
authors.forename: Risto
authors.initials: R
authors.lastname: Kaaja
authors.forename: Petri T
authors.initials: PT
authors.lastname: Kovanen
authors.forename: Jorma O
authors.initials: JO
authors.lastname: Kokkonen
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000503:physiopathology; D001794:Blood Pressure; D004195:Disease Models, Animal; D004452:Echocardiography; D005355:Fibrosis; D015870:Gene Expression; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology*; D017379:Hypertrophy, Left Ventricular / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000235:genetics*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D012333:RNA, Messenger; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; D014662:Vasoconstrictor Agents; D000804:Angiotensin II