Angiotensin II receptor antagonist, TCV-116, prevents myocardial hypertrophy in spontaneously hypertensive rats.
Recently, it has been suggested that angiotensin II (AII) might be associated with cardiac hypertrophy and fibrosis. We investigated the preventive effect of an AII receptor antagonist, TCV-116, on the development of cardiac hypertrophy and fibrosis in spontaneously hypertensive rats (SHR) at 24 weeks of age through histopathological study and an AII receptor assay. Treatment with TCV-116, enalapril (an angiotensin-converting enzyme inhibitor, ACEI), and hydralazine for 20 weeks lowered systolic blood pressure (SBP) significantly (-39 mmHg, -45 mmHg, and -45 mmHg, respectively). The heart weight/body weight ratio, cardiac myocyte diameter, and percent cardiac fibrosis were significantly reduced by treatment with TCV-116 and enalapril as compared with hydralazine treatment or no treatment. The AII receptor density was significantly increased by treatment with TCV-116 and enalapril as compared with hydralazine treatment or no treatment. The results of this study suggest that AII receptors are involved in the development of cardiac hypertrophy and fibrosis in SHR. It was demonstrated that the AII receptor antagonist, TCV-116, was comparable to the ACEI, enalapril, in inhibiting the progression of cardiac hypertrophy and fibrosis via the AII receptor.
Kagoshima
T
T
First Department of Internal Medicine, Nara Medical University, Kashihara, Japan.
Masuda
J
J
Sutani
T
T
Sakaguchi
Y
Y
Tsuchihashi
M
M
Tsuruta
S
S
Iwano
M
M
Dohi
K
K
Nakamura
Y
Y
Konishi
N
N
D000804:Angiotensin II / Q000097:blood / Q000378:metabolism; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D006332:Cardiomegaly / Q000473:pathology / Q000517:prevention & control*; D004719:Endomyocardial Fibrosis / Q000473:pathology / Q000517:prevention & control; D006973:Hypertension / Q000150:complications* / Q000188:drug therapy*; D007457:Iodine Radioisotopes; D007700:Kinetics; D009206:Myocardium / Q000648:ultrastructure; D011355:Prodrugs / Q000627:therapeutic use*; D051381:Rats; D011918:Rats, Inbred SHR; D011945:Receptors, Angiotensin / Q000378:metabolism; D013777:Tetrazoles
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D007457:Iodine Radioisotopes; D011355:Prodrugs; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; C077793:candesartan cilexetil