Intrarenal angiotensin II is associated with inflammation, renal damage, and dysfunction in Dahl salt-sensitive hypertension

The goal of this study was to test the hypothesis that intrarenal angiotensin (Ang) II has a proinflammatory effect leading to renal damage and dysfunction in Dahl salt-sensitive (S) rats on high-Na intake. Forty-six 7- to 8-week old Dahl S or Dahl salt-resistant (R)/Rapp strain rats were maintained for 5 weeks on high sodium (8%) with or without candesartan cilexetil in daily doses of 10 to 15 mg/kg/day. Arterial catheters were implanted at day 28. By day 35 in the high-Na S + candesartan rats, renal tissue Ang II concentration, renal monocytes/macrophages, tumor necrosis factor-α, and monocyte chemoattractant protein-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 with high-Na Dahl S rats, arterial pressure was unchanged in candesartan S rats, but creatinine clearance was increased. 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.