Angiotensin II receptor antagonist delays renal damage and stroke in salt-loaded Dahl salt-sensitive rats.
OBJECTIVE
To study the effects of blockade of the renin-angiotensin system upon the development of hypertension, end-organ damage and mortality in Dahl salt-sensitive (DSS) rats using an angiotensin II receptor antagonist, losartan.


METHODS
DSS rats (n = 186) were fed 8% NaCl from 6 to 16 weeks of age. One group received losartan whilst the control group was untreated. Changes in blood pressure and plasma renin activity (PRA), as well as renal and cerebrovascular damage and survival were assessed during the study.


RESULTS
Losartan blunted the blood pressure rise only transiently. Salt loading suppressed PRA in both groups until week 4 and thereafter it rose more markedly in the treated group. With no treatment renal lesions were first detected at 2 weeks, and strokes at 6 weeks. However, losartan transiently decreased the incidence and delayed the progression of renal damage and cerebrovascular lesions (strokes) and increased survival. PRA correlated with renal damage and the incidence of strokes in both groups. Blood pressure only partially affected survival, but did not correlate with stroke incidence.


CONCLUSIONS
These results indicate that whereas the rise in blood pressure is dependent upon sodium loading, morbidity and mortality in salt-loaded DSS rats are associated with activation of the renin-angiotensin system and are only partially related to blood pressure.
von Lutterotti
N
N
Department of Medicine, Cornell University Medical College, New York, NY 10021.
Camargo
M J
MJ
Campbell
W G
WG
Mueller
F B
FB
Timmermans
P B
PB
Sealey
J E
JE
Laragh
J H
JH
D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002561:Cerebrovascular Disorders / Q000209:etiology / Q000517:prevention & control*; D006973:Hypertension / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology*; D007674:Kidney Diseases / Q000209:etiology / Q000517:prevention & control*; D019808:Losartan; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System / Q000187:drug effects*; D012982:Sodium, Dietary; D016019:Survival Analysis; D013777:Tetrazoles / Q000494:pharmacology*
D001713:Biphenyl Compounds; D007093:Imidazoles; D012982:Sodium, Dietary; D013777:Tetrazoles; D000804:Angiotensin II; D019808:Losartan