AT1 receptor antagonist, TCV 116, does not prevent cardiac hypertrophy in salt-loaded Dahl salt-sensitive rats.
1. We investigated the effects of direct blockade of angiotensin II (AngII) by a potent, non-peptide angiotensin II toff 1 (AT1) receptor antagonist, TCV 116, on the development of cardiac hypertrophy in salt-loaded Dahl salt-sensitive rats. 2. Six week old male Dahl salt-sensitive rats (n = 44) were fed a 4% salt diet and were simultaneously given various doses of TCV 116 orally for 7 weeks. Each control group received vehicle alone. 3. Dietary high salt intake elevated blood pressure continuously and caused left ventricular hypertrophy in rats treated with vehicle. TCV 116 had a minor effect on the rise in blood pressure. Left ventricular mass (left ventricular weight/body-weight) decreased slightly but not significantly, in rats treated with 3 mg/kg per day of TCV 116 (n = 8). Higher doses of TCV 116 (6 and 10 mg/kg per day; n = 8 each) did not show a decrease in left ventricular mass compared with the vehicle control. 4. These results suggest that AngII blockade has only minor effects on hypertension and on cardiac hypertrophy in salt-loaded Dahl salt-sensitive rats and that the renin-angiotensin system may not contribute to the development of cardiac hypertrophy in Dahl salt-sensitive rats on a moderately high-salt diet.
Sugimoto
K
K
Second Department of Internal Medicine, Yokohama City University School of Medicine, Japan.
Gotoh
E
E
Takasaki
I
I
Ebina
T
T
Iwamoto
T
T
Takizawa
T
T
Shionoiri
H
H
Ishii
M
M
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D001835:Body Weight; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000188:drug therapy; D017379:Hypertrophy, Left Ventricular / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D011355:Prodrugs / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D012982:Sodium, Dietary / Q000009:adverse effects*; D013777:Tetrazoles
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D011355:Prodrugs; D012982:Sodium, Dietary; D013777:Tetrazoles; C077793:candesartan cilexetil