Chronic administration of angiotensin II receptor antagonist, TCV-116, in cardiomyopathic hamsters.
We examined whether specific blockade of the renin-angiotensin system is beneficial for the treatment of cardiac dysfunction in heart failure. The angiotensin II type-1 (AT1) receptor antagonist TCV-116 (10 mg.kg-1.day-1) or its vehicle was given orally to UM-X 7.1 cardiomyopathic (CM) and normal Golden Syrian (GS) hamsters for 8 wk. Plasma and cardiac angiotensin II levels were significantly higher in CM than in GS hamsters. The CM heart showed a smaller response of left ventricular (LV) pressure and first derivative of maximal LV pressure (+dP/dtmax) to the elevation of perfusion pressure (from 60 to 120 cmH2O) in Langendorff-perfused than in GS heart. Treatment with TCV-116 did not affect LV function in GS but significantly improved cardiac contractility in CM hamsters. These results suggest that the renin-angiotensin system plays an important role in the development of cardiac dysfunction due to cardiomyopathy. Blockade of this system by the AT1 antagonist TCV-116 appears to be useful in the prevention of heart failure.
Nakamura
F
F
Department of Geriatric Medicine, Osaka University Medical School, Suita, Japan.
Nagano
M
M
Kobayashi
R
R
Higaki
J
J
Mikami
H
H
Kawaguchi
N
N
Onishi
S
S
Ogihara
T
T
D000804:Angiotensin II / Q000097:blood / Q000378:metabolism; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001562:Benzimidazoles / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D009202:Cardiomyopathies / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006224:Cricetinae; D006168:Guinea Pigs; D006984:Hypertrophy; D008297:Male; D008647:Mesocricetus; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D011312:Pressure; D012084:Renin-Angiotensin System / Q000502:physiology; D013777:Tetrazoles; D016277:Ventricular Function, Left
D057911:Angiotensin Receptor Antagonists; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; D000804:Angiotensin II; C077793:candesartan cilexetil