Chronic angiotensin II antagonism with losartan in one-kidney, one clip hypertensive rats: effect on cardiac hypertrophy, urinary sodium and water excretion and the natriuretic system.
OBJECTIVE
To evaluate the effect of 7-day angiotensin II antagonism with losartan, an AT1-receptor antagonist, on systolic blood pressure, renal sodium and water excretion and on the atrial natriuretic factor system in one-kidney, one clip hypertensive rats.


METHODS
The one-kidney, one clip hypertensive rats were separated into four groups: untreated (group 1), low-sodium diet (group 2), losartan (20 mg/kg orally, group 3) and low-sodium diet with losartan (group 4). All of the rats were kept in metabolic cages with urinary volume, urinary sodium level and water intake being evaluated daily. Body weight and blood pressure were assessed before treatment and at the end of the observation period. Renal glomerular and papillary atrial natriuretic factor receptors were assessed by radioligand binding experiments.


RESULTS
No differences were observed either in body weight or in blood pressure between groups at the outset After 1 week, blood pressure was 184+/-4, 184+/-7, 170+/-5 and 78+/-8 mmHg, in groups 1, 2, 3 and 4, respectively. Group 3 rats failed to gain weight and had high urinary volume. In contrast, group 4 rats lost 15% of their original body weight. Both of the losartan-treated groups presented an apparently reduced cardiac hypertrophy but it was only clear in the low-sodium diet group. Both of the losartan-treated groups had high plasma renin activity. All of the three treated groups showed upregulation of glomerular and no changes in papillary atrial natriuretic factor receptors. Overall, mortality was 18, 27, 0 and 36% in groups 1, 2, 3 and 4, respectively.


CONCLUSIONS
Losartan administration reduces blood pressure in one-kidney, one clip rats only when combined with a low-sodium diet. Both low-sodium diet and angiotensin II antagonism upregulate renal glomerular but not papillary atrial natriuretic factor receptors, suggesting a divergent regulatory mechanism.
Garcia
R
R
Clinical Research Institute of Montréal, Université de Montréal, Québec, Canada.
Bonhomme
M C
MC
Diebold
S
S
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000037:antagonists & inhibitors* / Q000627:therapeutic use; D009320:Atrial Natriuretic Factor / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001834:Body Water / Q000187:drug effects / Q000378:metabolism; D006332:Cardiomegaly / Q000188:drug therapy; D002318:Cardiovascular Diseases; D004195:Disease Models, Animal; D004326:Drinking / Q000187:drug effects; D004336:Drug Antagonism; D006321:Heart / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy*; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects*; D019808:Losartan / Q000037:antagonists & inhibitors* / Q000627:therapeutic use; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000627:therapeutic use; D012083:Renin / Q000097:blood / Q000187:drug effects; D013997:Time Factors
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D009320:Atrial Natriuretic Factor; D012083:Renin; D019808:Losartan