Dose-dependent effect of ANG II-receptor antagonist on myocyte remodeling in rat cardiac hypertrophy.
The goal of this study was to examine the effect of an angiotensin II type 1 (AT1)-receptor antagonist (TCV-116) on left ventricular (LV) geometry and function during the development of pressure-overload LV hypertrophy. A low (LD; 0.3 mg x kg(-1) x day(-1)) or a high (HD; 3.0 mg x kg(-1) x day(-1)) dose of TCV-116 was administered to abdominal aortic-banded rats over 4 wk, and hemodynamics and morphology were then evaluated. In both LD and HD groups, peak LV pressures were decreased to a similar extent compared with the vehicle-treated group but stayed at higher levels than in the sham-operated group. In the LD group, both end-diastolic wall thickness (3.08 +/- 0.14 mm) and myocyte width (13.3 +/- 0.1 microm) decreased compared with those in the vehicle-treated group (3.67 +/- 0.19 mm and 15.3 +/- 0.1 microm, respectively; both P < 0.05). In the HD group, myocyte length was further decreased (HD: 82.6 +/- 2.6, LD: 94.1 +/- 2.9 microm; P < 0.05) in association with a reduction in LV midwall radius (HD: 3.36 +/- 0.12, LD: 3.60 +/- 0.14 mm; P < 0.05) and peak midwall fiber stress (HD: 69 +/- 8, LD: 83 +/- 10 x 10(3) dyn/cm2; P < 0.05). There was no significant difference in cardiac output among all groups. The AT1-receptor antagonist TCV-116 induced an inhibition of the development of pressure-overload hypertrophy. Morphologically, not only the width but also the length of myocytes was attenuated with TCV-116, leading to a reduction of midwall radius and hence wall stress, which in turn may contribute to a preservation of cardiac output.
Obayashi
M
M
Second Department of Internal Medicine, Yamaguchi University School of Medicine, Ube, Japan.
Yano
M
M
Kohno
M
M
Kobayashi
S
S
Tanigawa
T
T
Hironaka
K
K
Ryouke
T
T
Matsuzaki
M
M
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001794:Blood Pressure / Q000502:physiology; D001810:Blood Volume / Q000502:physiology; D006332:Cardiomegaly / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D018031:Connexin 43 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004548:Elasticity; D006321:Heart / Q000503:physiopathology; D006352:Heart Ventricles; D006439:Hemodynamics; D006973:Hypertension / Q000150:complications; D007150:Immunohistochemistry; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D013777:Tetrazoles; D016277:Ventricular Function, Left / Q000502:physiology
D057911:Angiotensin Receptor Antagonists; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D018031:Connexin 43; D013777:Tetrazoles; C077793:candesartan cilexetil