title: Losartan improved antioxidant defense, renal function and structure of postischemic hypertensive kidney.
abstract: Ischemic acute renal failure (ARF) is a highly complex disorder involving renal vasoconstriction, filtration failure, tubular obstruction, tubular backleak and generation of reactive oxygen species. Due to this complexity, the aim of our study was to explore effects of Angiotensin II type 1 receptor (AT1R) blockade on kidney structure and function, as well as oxidative stress in spontaneously hypertensive rats (SHR) after renal ischemia reperfusion injury. Experiments were performed on anaesthetized adult male SHR in the model of ARF with 40 minutes clamping the left renal artery. The right kidney was removed and 40 minutes renal ischemia was performed. Experimental groups received AT1R antagonist (Losartan) or vehicle (saline) in the femoral vein 5 minutes before, during and 175 minutes after the period of ischemia. Biochemical parameters were measured and kidney specimens were collected 24 h after reperfusion. ARF significantly decreased creatinine and urea clearance, increased LDL and lipid peroxidation in plasma. Treatment with losartan induced a significant increase of creatinine and urea clearance, as well as HDL. Lipid peroxidation in plasma was decreased and catalase enzyme activity in erythrocytes was increased after losartan treatment. Losartan reduced cortico-medullary necrosis and tubular dilatation in the kidney. High expression of pro-apoptotic Bax protein in the injured kidney was downregulated after losartan treatment. Our results reveal that angiotensin II (via AT1R) mediates the most postischemic injuries in hypertensive kidney through oxidative stress enhancement. Therefore, blockade of AT1R may have beneficial effects in hypertensive patients who have developed ARF.
authors.affiliation: Department of Cardiovascular Physiology, Institute for Medical Research, University of Belgrade, Belgrade, Serbia.
authors.forename: Milan
authors.initials: M
authors.lastname: Ivanov
authors.affiliation: Department of Cardiovascular Physiology, Institute for Medical Research, University of Belgrade, Belgrade, Serbia.
authors.forename: Nevena
authors.initials: N
authors.lastname: Mihailović-Stanojević
authors.affiliation: Department of Cardiovascular Physiology, Institute for Medical Research, University of Belgrade, Belgrade, Serbia.
authors.forename: Jelica
authors.initials: J
authors.lastname: Grujić Milanović
authors.affiliation: Department of Cardiovascular Physiology, Institute for Medical Research, University of Belgrade, Belgrade, Serbia.
authors.forename: Đurđica
authors.initials: Đ
authors.lastname: Jovović
authors.affiliation: Institute of Pathology, Medical Faculty, University of Belgrade, Belgrade, Serbia.
authors.forename: Jasmina
authors.initials: J
authors.lastname: Marković-Lipkovski
authors.affiliation: Institute of Pathology, Medical Faculty, University of Belgrade, Belgrade, Serbia.
authors.forename: Sanja
authors.initials: S
authors.lastname: Ćirović
authors.affiliation: Department of Cardiovascular Physiology, Institute for Medical Research, University of Belgrade, Belgrade, Serbia.
authors.forename: Zoran
authors.initials: Z
authors.lastname: Miloradović
mesh_terms: D057911:Angiotensin Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002374:Catalase / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003404:Creatinine / Q000378:metabolism; D015536:Down-Regulation; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D007677:Kidney Function Tests; D015227:Lipid Peroxidation; D019808:Losartan / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D011918:Rats, Inbred SHR; D015427:Reperfusion Injury / Q000188:drug therapy*; D014508:Urea / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D057911:Angiotensin Receptor Antagonists; D000975:Antioxidants; C494828:Bax protein, rat; D008078:Cholesterol, LDL; D051028:bcl-2-Associated X Protein; D014508:Urea; D003404:Creatinine; D002374:Catalase; D019808:Losartan