Author(s): Lin L, Phillips WE, Manning RD
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Abstract 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.
This article was published in J Am Soc Hypertens
and referenced in Journal of Clinical & Experimental Cardiology