Low-dose candesartan improves renal blood flow and kidney oxygen tension in rats with endotoxin-induced acute kidney...

Sepsis is associated with an activation of the renin-angiotensin system and causes acute kidney injury. The aim was to examine the effects of a low, nondepressor dose of the selective angiotensin II type 1 receptor antagonist candesartan on renal hemodynamics and function in endotoxemic rats. Endotoxemia was induced in Sprague-Dawley rats by a dose of LPS (Escherichia coli O127:B8; 7.5 mg kg(-1), i.p.). At 16 h after endotoxin administration, renal clearance experiments were performed in thiobutabarbital anesthetized rats. Study groups (1) sham-saline, (2) LPS-saline, and (3) LPS-candesartan received isotonic saline or candesartan (10 microg kg(-1), i.v.) after baseline measurements. Kidney function, renal blood flow (RBF), and cortical and outer medullary perfusion (laser-Doppler flowmetry) and oxygen tension (P(O2); Clark-type microelectrodes) were analyzed during 2 h after drug administration. At baseline, endotoxemic rats showed an approximately 50% reduction in glomerular filtration rate and RBF (P < 0.05), a decline in cortical and outer medullary perfusion, and Po2 (P < 0.05), but no significant alterations in MAP compared with saline-injected controls. Candesartan treatment significantly improved RBF (+40% +/- 6% vs. baseline), cortical perfusion (+18% +/- 3% vs. baseline), and cortical (+19% +/- 7% vs. baseline) and outer medullary (+22% +/- 10% vs. baseline) P(O2) in endotoxemic rats (P < 0.05 vs. LPS-saline). Candesartan did not significantly influence MAP or glomerular filtration rate, whereas filtration fraction was reduced by 27% +/- 5% vs. baseline (P < 0.05 vs. LPS-saline). In conclusion, candesartan, in a dose that did not significantly decrease MAP, caused renal vasodilation and markedly improved RBF and intrarenal P(O2) in endotoxemic rats. These findings suggest renoprotective effects of candesartan in sepsis.