Intrarenal Angiotensin ii is associated with inflammation, renal damage and dysfunction in dahl salt-sensitive hypertension.
BACKGROUND
The goal of this study was to test the hypothesis that intrarenal Ang II has a proinflammatory effect leading to renal damage and dysfunction in Dahl S rats on high Na intake.


METHODS
Forty-six 7-to 8-week old Dahl S or R/Rapp strain rats were maintained for 5 weeks on high sodium (8%) with or without candesartan cilexetil in daily doses of 10-15 mg/kg/day. Arterial catheters were implanted at day 28.


RESULTS
By day 35 in the high Na S + candesartan rats, renal tissue Ang II concentration, renal monocytes/macrophages, TNFalpha, and MCP-1 significantly decreased. Plasma Ang II remained at very low levels in all groups. Reduced renal damage in candesartan-treated Dahl S rats was demonstrated by marked decreases in urinary protein excretion and renal glomerular and interstitial damage. After 5 weeks of high Na, compared to high Na Dahl S rats, arterial pressure was unchanged in candesartan S rats, but creatinine clearance was increased.


CONCLUSIONS
Therefore, candesartan reduced renal tissue Ang II, renal damage, infiltration of immune cells, cytokines, chemokines, and improved renal hemodynamics. These data suggest that intrarenal Ang II plays an important role in causing renal inflammation which leads to renal cortical damage, proteinuria, and decreases in renal hemodynamics.
Lin
L
L
Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi.
Phillips
W E
WE
Manning
R D
RD