title: Angiotensin 2 type 1 receptor blockade different affects postishemic kidney injury in normotensive and hypertensive rats.
abstract: Many studies demonstrated that angiotensin 2 type 1 receptor (AT1R) blockade accelerates renal recovery in post-ischaemic kidney but there are many controversies related to its net effect on kidney structure and function. During the past years, our research group was trying to define the pathophysiological significance of the renin-angiotensin system on post-ischemic acute renal failure (ARF) development in normotensive Wistar as well as hypertensive rats (SHR). This review mostly summarizes our experience in that field. Our previous studies in normotensive rats revealed that AT1R blockade, except slightly renal vascular resistance improvement, had no other obvious beneficial effects, and therefore implies angiotensin 2 (Ang-2) overexpression as non-dominant on kidney reperfusion injuries development. Similarly it was observed in Wistar rats with induced mild (L-NAME, 3 mg/kg b.w.) nitric oxide (NO) deficiency. Expectably, in strong induced (L-NAME, 10 mg/kg b.w.) NO deficiency associated with ARF, massive tubular injuries indicate harmful effects of AT1R blockade, implying strongly disturbed glomerular filtration and suggesting special precaution related to AT1R blockers usage. Opposite to previous, by our opinion, AT1R antagonism promises new advance in treatment of essentially hypertensive subjects who develop ARF. Increased glomerular filtration, diminished oxidative stress, and most importantly improved tubular structure in postishemic SHR treated with AT1R blocker losartan, implicate Ang-2 over production as potently agent in the kidney ischemic injury, partly trough generation of reactive oxygen species. These data contribute understanding the pathogenesis of this devastating illness in hypertensive surroundings.
authors.affiliation: Institute for Medical Research University of Belgrade, Dr Subotića 4, PO Box 102, Belgrade, 11129, Serbia. zokim@imi.bg.ac.rs.
authors.forename: Zoran
authors.initials: Z
authors.lastname: Miloradović
authors.affiliation: Institute for Medical Research University of Belgrade, Dr Subotića 4, PO Box 102, Belgrade, 11129, Serbia.
authors.forename: Milan
authors.initials: M
authors.lastname: Ivanov
authors.affiliation: Institute for Medical Research University of Belgrade, Dr Subotića 4, PO Box 102, Belgrade, 11129, Serbia.
authors.forename: Đurđica
authors.initials: Đ
authors.lastname: Jovović
authors.affiliation: Institute for Medical Research University of Belgrade, Dr Subotića 4, PO Box 102, Belgrade, 11129, Serbia.
authors.forename: Danijela
authors.initials: D
authors.lastname: Karanović
authors.affiliation: Institute for Medical Research University of Belgrade, Dr Subotića 4, PO Box 102, Belgrade, 11129, Serbia.
authors.forename: Una Jovana
authors.initials: UJ
authors.lastname: Vajić
authors.affiliation: Institute of Pathology, Medical School University of Belgrade, Belgrade, Serbia.
authors.forename: Jasmina
authors.initials: J
authors.lastname: Marković-Lipkovski
authors.affiliation: Institute for Medical Research University of Belgrade, Dr Subotića 4, PO Box 102, Belgrade, 11129, Serbia.
authors.forename: Nevena
authors.initials: N
authors.lastname: Mihailović-Stanojević
authors.affiliation: Institute for Medical Research University of Belgrade, Dr Subotića 4, PO Box 102, Belgrade, 11129, Serbia.
authors.forename: Jelica Grujić
authors.initials: JG
authors.lastname: Milanović
mesh_terms: D058186:Acute Kidney Injury / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D005786:Gene Expression Regulation; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D019808:Losartan / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism; D012077:Renal Artery / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000235:genetics; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D017382:Reactive Oxygen Species; D044140:Receptor, Angiotensin, Type 1; D009569:Nitric Oxide; D019808:Losartan
keywords: Experimental; Hypertension; Losartan; Normotension; Postishemic kidney injury