title: Low-dose candesartan improves renal blood flow and kidney oxygen tension in rats with endotoxin-induced acute kidney dysfunction.
abstract: 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.
authors: Department of Anesthesiology and Intensive Care, Institute of Clinical Sciences, Sahlgrenska University Hospital, Göteborg, Sweden. nicoletta.nitescu@vgregion.se
authors: Nicoletta
authors: N
authors: Nitescu
authors: Elisabeth
authors: E
authors: Grimberg
authors: Gregor
authors: G
authors: Guron
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology*; D001713:Biphenyl Compounds; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D010100:Oxygen / Q000097:blood*; D010101:Oxygen Consumption / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects* / Q000502:physiology; D013777:Tetrazoles / Q000494:pharmacology*
chemical_list: D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D008070:Lipopolysaccharides; D013777:Tetrazoles; D010100:Oxygen; C081643:candesartan