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Pathophysiological role of intrarenal Angiotensin II (AngII) in Dahl salt‐sensitive (SS) hypertensive rats
Author(s) -
Mattson David,
Lund Hayley
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.735.3
Subject(s) - medicine , endocrinology , losartan , angiotensin ii , renin–angiotensin system , albuminuria , kidney , captopril , plasma renin activity , chemistry , angiotensin ii receptor type 1 , sodium , receptor , blood pressure , organic chemistry
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.