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 wi th losartan, an AT(1)-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-kid ney, one clip hypertensive rats were separated into four groups: untre ated (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 pressur e were assessed before treatment and at the end of the observation per iod, Renal glomerular and papillary atrial natriuretic factor receptor s were assessed by radioligand binding experiments. Results No differe nces 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, respectiv ely, Group 3 rats failed to gain weight and had high urinary volume, I n 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 chan ges in papillary atrial natriuretic factor receptors, Overall, mortali ty was 18, 27, 0 and 36% in groups 1, 2, 3 and 4, respectively. Conclu sion 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.