Angiotensin II receptor antagonist markedly reduces mortality in salt-loaded Dahl S rats.
We investigated the effect of blockade of the renin-angiotensin system (RAS) on morbidity and hypertension in salt-loaded Dahl salt-sensitive (Dahl S) rats. Six-week-old male Dahl S rats (n = 198) were fed a high sodium diet (8% NaCl) for 10 weeks. One group of rats (n = 91) was treated with 30 mg/kg/day of the nonpeptide angiotensin II receptor antagonist, DuP 753, whereas the control group (n = 107) was left untreated. Blood pressure rose steeply in both groups, reaching levels above 200 mm Hg by week 6. DuP 753-treated animals were less hypertensive than controls between weeks 3 and 5 of the study, but had similar blood pressure before and after that time. Although the angiotensin II antagonist had only a transient effect on blood pressure it markedly prolonged survival. After 10 weeks, 68.3% of rats receiving DuP 753, but only 30.1% of controls, were still alive (P less than .0001). Higher morbidity in controls than in DuP 753-treated rats was also suggested by body weights. Following 6 weeks of high salt diet, untreated rats progressively lost weight while DuP 753-treated animals maintained a steady body weight. These results show that the angiotensin II receptor antagonist DuP 753 greatly enhanced survival in salt-loaded Dahl S rats although it reduced blood pressure only transiently. Our data are consistent with a contribution of the RAS to morbidity in this model of hypertension.
von Lutterotti
N
N
Cardiovascular and Hypertension Center, Cornell University Medical College, New York, NY 10021.
Camargo
M J
MJ
Mueller
F B
FB
Timmermans
P B
PB
Laragh
J H
JH
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy* / Q000401:mortality; D007093:Imidazoles / Q000627:therapeutic use*; D019808:Losartan; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012982:Sodium, Dietary / Q000037:antagonists & inhibitors; D015996:Survival Rate; D013777:Tetrazoles / Q000627:therapeutic use*
D057911:Angiotensin Receptor Antagonists; D007093:Imidazoles; D012982:Sodium, Dietary; D013777:Tetrazoles; D019808:Losartan