title: Apoptosis, myocardial fibrosis and angiotensin II in the left ventricle of hypertensive rats treated with fosinopril or losartan.
abstract: OBJECTIVE
  To investigate the different effects of an angiotensin II type 1 (AT(1)) receptor antagonist, losartan, and an angiotensin converting enzyme (ACE) inhibitor, fosinopril, on cardiomyocyte apoptosis, myocardial fibrosis, and angiotensin II (Ang II) in the left ventricle of spontaneously hypertensive rats (SHRs).
  
  
  METHODS
  SHRs of 16-week-old were randomly divided into 3 groups: SHR-L (treated with losartan, 30 mg.kg(-1) x d(-1)), SHR-F (treated with fosinopril, 10 mg x kg(-1) x d(-1)), and SHR-C (treated with placebo). Each group consisted of 10 rats. Five rats, randomly selected from each group, were killed at the 8th and 16th week after treatment. Cardiomyocyte apoptosis, collagen volume fraction (CVF), perivascular collagen area (PVCA) and Ang II concentrations of plasma and myocardium were examined.
  
  
  RESULTS
  Compared with the controls at the 8th and 16th week, systolic blood pressures were similarly decreased in both treatment groups. Left ventricular weight and left ventricular mass indexes were significantly lower in both treatment groups. However, the latter parameter at the 16th week was reduced to a less extent in the fosinopril group than that in the losartan group. Compared with the controls, cardiomycyte apoptotic index was significantly reduced at the 8th week only in the fosinopril group, and at the 16th week in both treatment groups. The index of the fosinopril group was lower than that of the losartan group at the latter endpoint examined. Compared with the controls, the left ventricular collagen volume fraction and perivascular collagen area at the 8th and 16th weeks were significantly reduced in the SHRs treated with either fosinopril or losartan. However, the collagen volume fraction at the latter endpoint in the fosinopril group was lower than that in the losartan group. Compared with the controls at endpoints, plasma and myocardium Ang II levels were significantly increased in the losartan group. However, plasma Ang II concentrations were not altered, and myocardium Ang II concentrations at the 8th and 16th weeks were significantly reduced in the fosinopril group.
  
  
  CONCLUSIONS
  Both losartan and fosinopril could effectively inhibit cardiomyocyte apoptosis and myocardial fibrosis and reverse heart hypertrophy. Fosinopril may be more effective in these cardioprotective effects, suggesting that the effects of both drugs are related to the inhibition of myocardium renin-angiotension-aldsterone system.
authors.affiliation: Department of Geriatric Cardiology, Xiangya Hospital, Hunan Medical University, Changsha 410008, China.
authors.forename: Guolong
authors.initials: G
authors.lastname: Yu
authors.forename: Xiaoqiu
authors.initials: X
authors.lastname: Liang
authors.forename: Xiumei
authors.initials: X
authors.lastname: Xie
authors.forename: Tianlun
authors.initials: T
authors.lastname: Yang
authors.forename: Ming
authors.initials: M
authors.lastname: Sun
authors.forename: Shuiping
authors.initials: S
authors.lastname: Zhao
mesh_terms: D000804:Angiotensin II / Q000032:analysis*; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D005355:Fibrosis; D017328:Fosinopril / Q000627:therapeutic use*; D006973:Hypertension / Q000150:complications / Q000188:drug therapy*; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy*; D019808:Losartan / Q000627:therapeutic use*; D009206:Myocardium / Q000737:chemistry / Q000473:pathology*; D051381:Rats; D011918:Rats, Inbred SHR
chemical_list: D000959:Antihypertensive Agents; D000804:Angiotensin II; D019808:Losartan; D017328:Fosinopril