Effects of the AT1-receptor antagonist eprosartan on the progression of left ventricular dysfunction in dogs with heart failure.
1. We examined the effects of eprosartan, an AT(1) receptor antagonist, on the progression of left ventricular (LV) dysfunction and remodelling in dogs with heart failure (HF) produced by intracoronary microembolizations (LV ejection fraction, EF 30 to 40%). 2. Dogs were randomized to 3 months of oral therapy with low-dose eprosartan (600 mg once daily, n=8), high-dose eprosartan (1200 mg once daily, n=8), or placebo (n=8). 3. In the placebo group, LV end-diastolic (EDV) and end-systolic (ESV) volumes increased after 3 months (68+/-7 vs 82+/-9 ml, P<0.004, 43+/-1 vs 58+/-7 ml, P<0.003, respectively), and EF decreased (37+/-1 vs 29+/-1%, P<0.001). In dogs treated with low-dose eprosartan, EF, EDV, and ESV remained unchanged over the course of therapy, whereas in dogs treated with high-dose eprosartan, EF increased (38+/-1 vs 42+/-1%, P<0.004) and ESV decreased (41+/-1 vs 37+/-1 ml, P<0.006), Eprosartan also decreased interstitial fibrosis and cardiomyocyte hypertrophy. 4. We conclude that eprosartan prevents progressive LV dysfunction and attenuates progressive LV remodelling in dogs with moderate HF and may be useful in treating patients with chronic HF.
Suzuki
George
G
Department of Medicine, Division of Cardiovascular Medicine, Henry Ford Heart & Vascular Institute, Detroit, Michigan 48202, U.S.A.
Mishima
Takayuki
T
Tanhehco
Elaine J
EJ
Sharov
Victor G
VG
Todor
Anastassia
A
Rostogi
Sharad
S
Gupta
Ramesh C
RC
Chaudhry
Pervaiz A
PA
Anagnostopoulos
Petros V
PV
Nass
Omar
O
Goldstein
Sidney
S
Sabbah
Hani N
HN
D000179:Acrylates / Q000494:pharmacology / Q000627:therapeutic use*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D018450:Disease Progression; D004285:Dogs; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000502:physiology; D013876:Thiophenes; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy* / Q000503:physiopathology
D000179:Acrylates; D057911:Angiotensin Receptor Antagonists; D007093:Imidazoles; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D013876:Thiophenes; C068373:eprosartan