Beneficial effects of long-term enalapril treatment and low-salt intake on survival rate of dahl salt-sensitive rats with established hypertension.
We investigated the effects of long-term treatment with the angiotensin-converting enzyme inhibitor enalapril and low-salt intake on the survival rate of Dahl salt-sensitive rats fed a high-salt (6.0% NaCl) diet. The systolic blood pressure of the rats increased gradually from 5 weeks of age and reached >240 mm Hg at 12 weeks of age. At this point, a low-salt diet group received a placebo (group 1, n = 10), and the high-salt diet group was divided into three groups: those given a placebo with the high-salt diet (group 2, n = 15), those given a chow change from a high- to a low-salt diet with a placebo (group 3, n = 14) and those given enalapril (30 mg/kg/day p.o., group 4, n = 14). At 19 weeks of age, all rats in group 1 were alive, and the survival rate of group 2 was only 40% (P < .001 vs. group 1). The survival rates of both groups 3 and 4 were significantly better: 86% (P < .01 vs. group 2) and 93% (P < .01), respectively. This beneficial effect on mortality was accompanied by an amelioration of the elevated plasma creatinine and urea nitrogen levels and a decrease in the glomerular sclerosis lesion scores in both groups. These results suggested that a high-salt content diet and the renin-angiotensin system are deterioration factors in lethal renal damage and the limitation of the diet salt content and inhibition of the renin-angiotensin system are important to improve the survival rate in high-salt-loaded hypertensive Dahl salt-sensitive rats.
Kodama
K
K
Cardiovascular Research Unit, and Drug Safety Research Laboratory, Tsukuba Research Laboratories, Eisai Co., Ltd., Tsukuba, Ibaraki 300-26, Japan.
Adachi
H
H
Sonoda
J
J
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004656:Enalapril / Q000627:therapeutic use*; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D007668:Kidney / Q000473:pathology; D008297:Male; D051381:Rats; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage*; D015996:Survival Rate
D000806:Angiotensin-Converting Enzyme Inhibitors; D017673:Sodium Chloride, Dietary; D004656:Enalapril