title: Angiotensin II augments medullary hypoxia and predisposes to acute renal failure.
abstract: The effects of angiotensin II (AII) upon medullary hypoxic injury and kidney function were investigated in vitro and in vivo. Synthetic AII added to perfusate of isolated rat kidneys reduced perfusion flow from 48 +/- 2 ml min-1 (+/- SE) to 19 +/- 1 (P less than 0.001) without altering glomerular filtration rate (GFR), raising filtration fraction from 1% to 3% (P less than 0.001). AII-extended hypoxic injury to medullary thick ascending limbs (mTAL) from 66 +/- 4% of tubules to 79 +/- 3 (P less than 0.05) in correlation with filtration fraction (r = 0.8, P less than 0.001). Addition of indomethacin (10(-4) mol l-1) further extended medullary hypoxic damage to 89 +/- 2% of mTAL (P less than 0.001). Uninephrectomized rats kept in metabolic cages were given AII by continuous infusion (0.1-0.8 microgram min-1) and indomethacin (10 mg kg-1 day-1) for 24 h. Creatinine clearance declined from 1.3 +/- 0.1 ml min-1 to 0.6 +/- 0.06 (P less than 0.001). Morphological examination revealed either selective necrosis of mTAL (in 12 +/- 4% of tubules) or luminal collapse (in 63 +/- 8%). Both necrosis and collapse correlated inversely with creatinine clearance and with each other (r = -0.5, P less than 0.001), the latter correlation suggesting protection from hypoxic injury by cessation of solute delivery. By increasing filtration fraction and decreasing blood flow, AII decreases renal oxygen supply while maintaining oxygen consumption for solute reabsorption. AII may predispose to acute renal failure by augmenting medullary hypoxia.
authors.affiliation: Department of Medicine, Hadassah University Hospital, Jerusalem, Israel.
authors.forename: M
authors.initials: M
authors.lastname: Brezis
authors.forename: Z
authors.initials: Z
authors.lastname: Greenfeld
authors.forename: A
authors.initials: A
authors.lastname: Shina
authors.forename: S
authors.initials: S
authors.lastname: Rosen
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology*; D000804:Angiotensin II / Q000494:pharmacology* / Q000502:physiology; D000818:Animals; D005919:Glomerular Filtration Rate / Q000187:drug effects; D000860:Hypoxia / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D066298:In Vitro Techniques; D007679:Kidney Medulla / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010101:Oxygen Consumption / Q000187:drug effects; D010477:Perfusion; D051381:Rats; D012079:Renal Circulation / Q000187:drug effects
chemical_list: D000804:Angiotensin II