Pathophysiological role of intrarenal Angiotensin II (AngII) in Dahl salt‐sensitive (SS) hypertensive rats

Abstract

Experiments investigated the role of intrarenal AngII in normotensive and salt‐sensitive hypertensive rats. Increasing dietary NaCl from 0.4% to 4.0% in normal Sprague Dawley rats (n=4–7/group) significantly suppressed plasma renin concentration (5.3±1.3 to 2.9±0.7 ng AngI/ml/hr), plasma AngII (11.7±2.2 to 6.2±0.8 pg/ml), and renal tissue AngII (84±12 to 37±6 pg/gram tissue). The ratio of kidney to plasma AngII was unaltered from the 0.4% NaCl value of 7.2±1.0 when sodium intake was increased. In contrast, increasing dietary NaCl from 0.4 to 4.0% in Dahl SS significantly decreased kidney renin concentration (from 1343±247 to 527±142 ng AngI/μg protein/hr) but the ratio of kidney to plasma AngII significantly increased from 5.9±1.1 to 10.8±2.9. Experiments were then performed to evaluate the functional role of the elevated intrarenal AngII in Dahl SS rats fed high salt. Compared to vehicle‐treated SS rats fed 4.0% NaCl, administration of the AT1 receptor antagonist losartan (30 mg/kg/day, oral) to Dahl SS rats led to a significant attenuation of salt‐sensitive hypertension from 163±6 to 137±1 mmHg and albuminuria from 62±12 to 30±5 mg/day. Administration of captopril (15 mg/kg/day, oral) had similar effects on hypertension and albuminuria in Dahl SS fed high salt. These studies indicate that inappropriately elevated intrarenal AngII may participate in the development of Dahl SS hypertension.