Comparative effects of an angiotensin-converting enzyme inhibitor and an angiotensin II antagonist in Dahl rats.
The antihypertensive, cardioprotective, and renoprotective effects of a nonpeptide angiotensin II antagonist (AIIA, CV-11974) and an angiotensin-converting enzyme inhibitor (CEI, captopril) were compared in Dahl salt-sensitive rats. Six-week-old male rats received a high-salt diet (4% NaCl) and were divided into control, CEI, and AIIA groups. The CEI group received captopril (15 mg/kg/day) and the AIIA group received CV-11974 (0.72 mg/kg/day), an active metabolite of the AIIA TCV-116, for 4 weeks by continuous subcutaneous infusion. After 4 weeks, systolic blood pressure (SBP) was significantly lower in the treatment groups than in the control group. The heart weight/body weight ratio and urinary protein excretion were reduced in the treatment groups, and renal damage (glomerular sclerosis score) was reduced by approximately 50%. CV-11974 and captopril were comparable in reducing BP, cardiac hypertrophy, and renal damage, suggesting that the renin-angiotensin (R-A) system is involved in elevating BP and promoting cardiovascular damage, despite suppression of the R-A system in this model. The antihypertensive effect of CEI may be due primarily to inhibition of the action of angiotensin II, while other effects, e.g., potentiation of the kinin system, may be less important.
Ideishi
M
M
Department of Internal Medicine, Fukuoka University School of Medicine, Japan.
Miura
S
S
Sakai
T
T
Maeda
H
H
Kinoshita
A
A
Sasaguri
M
M
Jimi
S
S
Arakawa
K
K
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology*; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012680:Sensitivity and Specificity; D012965:Sodium Chloride / Q000008:administration & dosage; D013777:Tetrazoles / Q000494:pharmacology*
D057911:Angiotensin Receptor Antagonists; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; D012965:Sodium Chloride; D002216:Captopril; C081643:candesartan; D009638:Norepinephrine