title: Pressure overload per se rather than cardiac angiotensin converting enzyme activity may be important in the development of rat cardiac hypertrophy.
abstract: OBJECTIVE
  To investigate the roles of the renin-angiotensin system and blood pressure in cardiac hypertrophy caused by a pressure overload.
  
  
  METHODS
  Cardiac hypertrophy was induced by constricting the abdominal aorta above the renal arteries. After they had been banded, the rats were treated with the lower (1 mg/kg per day) or the higher (10 mg/kg per day) dose of quinapril [an angiotensin converting enzyme (ACE) inhibitor], or the lower (1 mg/kg per day) or the higher (10 mg/kg per day) dose of TCV-116 [an angiotensin II (AngII) AT1 receptor antagonist], for 4 weeks. Then, we measured the mean blood pressure (MBP), body weight, left ventricular weight (LVW), and serum and cardiac ACE activities.
  
  
  RESULTS
  The higher dose of quinapril and that of TCV-116 prevented left ventricular hypertrophy and MBP elevation. Both the higher and the lower doses of quinapril reduced the serum and cardiac ACE activities significantly, whereas the higher dose of TCV-116 reduced the cardiac ACE activity and increased the serum ACE activity. The lower dose of quinapril, however, exerted no significant effect on MBP and the LVW:body weight ratio, although it reduced the cardiac and serum ACE activities significantly. There was a significant positive correlation between the MBP and the LVW:body weight ratio regardless of the cardiac ACE activity in data from all groups (r = 0.676, P < 0.0001).
  
  
  CONCLUSIONS
  Our data indicate the importance of the blood pressure as a determinant of cardiac hypertrophy because inhibition of cardiac ACE activity alone without lowering of the blood pressure is insufficient to prevent cardiac hypertrophy. Our results suggest the presence of other pathways for AngII production not mediated by ACE, or growth factors other than AngII in pressure-overload cardiac hypertrophy.
authors.affiliation: Department of Internal Medicine II, Nagoya University School of Medicine, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Mukawa
authors.forename: Y
authors.initials: Y
authors.lastname: Toki
authors.forename: A
authors.initials: A
authors.lastname: Shimauchi
authors.forename: H
authors.initials: H
authors.lastname: Matsui
authors.forename: I
authors.initials: I
authors.lastname: Morishima
authors.forename: K
authors.initials: K
authors.lastname: Okumura
authors.forename: T
authors.initials: T
authors.lastname: Ito
authors.forename: T
authors.initials: T
authors.lastname: Hayakawa
mesh_terms: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage; D001562:Benzimidazoles / Q000008:administration & dosage; D001713:Biphenyl Compounds / Q000008:administration & dosage; D001794:Blood Pressure / Q000187:drug effects; D006332:Cardiomegaly / Q000209:etiology*; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism; D007546:Isoquinolines / Q000008:administration & dosage; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000378:metabolism*; D000077583:Quinapril; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D044005:Tetrahydroisoquinolines; D013777:Tetrazoles
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D007546:Isoquinolines; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D044005:Tetrahydroisoquinolines; D013777:Tetrazoles; D007703:Peptidyl-Dipeptidase A; C077793:candesartan cilexetil; D000077583:Quinapril