Enhancement of Intrarenal Angiotensinogen in Dahl Salt-Sensitive Rats on High Salt Diet

Abstract

This study was performed to examine whether there is an inappropriate regulation of intrarenal angiotensinogen in Dahl-salt sensitive rats (DS) fed a high salt diet (HS). Dahl salt-resistant rats (DR) and DS were maintained on HS (8% NaCl) or low salt diet (LS, 0.3% NaCl) for 4 weeks. Systolic blood pressure (SBP), measured by tail-cuff plethysmography, was unaltered in DR (DR+HS, 127±3 mm Hg, n=5; DR+LS, 126±3, n=5); however, SBP was significantly increased in DS+HS (208±7, n=9) compared with DS+LS (134±2, n=5). HS suppressed plasma renin activity in both strains (0.7±0.2 ng of angiotensin I/mL per hour in DS+HS, 3.1±0.5 in DS+LS, 0.8±0.2 in DR+HS, 5.1±0.7 in DR+LS). Plasma angiotensinogen levels, measured by Western blot analysis, were also suppressed by HS in both strains (36 919±2170 integrated densitometric unit in DS+HS, 53 028±2752 in DS+LS, 44 722±1721 in DR+HS, 55782±3785 in DR+LS). However, kidney angiotensinogen levels were significantly increased in DS+HS (75 850±4171, integrated densitometric unit) compared with DS+LS (47 232±3470), DR+HS (44 748±8236), and DR+LS (42 504±4052). Urinary excretion of angiotensinogen, measured by radioimmunoassay of angiotensin I after incubation with excess renin, had a similar profile. Urinary excretion of angiotensinogen was significantly increased in DS+HS (2958±531 pmol/d) compared with DS+LS (56±4), DR+HS (31±12), and DR+LS (21±7). These data indicate that intrarenal angiotensinogen is enhanced in DS+HS, which is reflected by the increased urinary excretion of angiotensinogen. The results suggest that DS on HS have an inappropriate augmentation of intrarenal angiotensinogen, which may contribute to impaired sodium excretion during a high salt diet and the development of hypertension in this strain.