title: Compensated heart failure predisposes to outer medullary tubular injury: studies in rats.
abstract: BACKGROUND
  Heart failure (HF) is considered a putative factor predisposing to acute renal failure (ARF). Since outer medullary hypoxic injury may play an important role in the pathogenesis of acute tubular necrosis, we explored the impact of experimental HF on the propensity to develop ARF with hypoxic medullary injury following the inhibition of prostaglandin and nitric oxide synthesis.
  
  
  METHODS
  Compensated, high-output HF was induced in Sprague-Dawley rats by aorto-caval fistula. At the eighth to ninth postoperative day, the rats were injected with indomethacin and N(omega) nitro-L-arginine methyl ester (L-NAME; ARF protocol) and were sacrificed 24 hours later for morphologic evaluation.
  
  
  RESULTS
  Kidney function comparably declined in HF-ARF rats and in control sham operated animals (CTR-ARF). Nevertheless, outer medullary hypoxic damage with medullary thick ascending limb (mTAL) necrosis occurred almost exclusively in the HF-ARF group (11 +/- 4% vs. 0.2 +/- 0.2% of tubules in CTR-ARF, P < 0.03). In a third group of HF animals subjected to vehicles only (HF-Nil), kidney function was preserved and renal morphology remained intact. Papillary-tip necrosis was consistently found in all animals subjected to indomethacin and L-NAME, irrespective of preconditioning. Morphometric evaluation disclosed that HF was not associated with mTAL hypertrophy.
  
  
  CONCLUSIONS
  Incipient HF predisposes to hypoxic outer medullary injury, probably reflecting the impact of regional vasoconstrictive stimuli rather than tubular hypertrophy when protective local vasodilating mechanisms are hampered. The presence and extent of outer medullary hypoxic damage cannot be predicted from the functional derangement, which in the experimental settings may also represent prerenal azotemia or papillary damage.
authors.affiliation: The Nephrology Unit, Bikur Holim Hospital, Jerusalem, Israel.
authors.forename: M
authors.initials: M
authors.lastname: Goldfarb
authors.forename: Z
authors.initials: Z
authors.lastname: Abassi
authors.forename: S
authors.initials: S
authors.lastname: Rosen
authors.forename: A
authors.initials: A
authors.lastname: Shina
authors.forename: M
authors.initials: M
authors.lastname: Brezis
authors.forename: S N
authors.initials: SN
authors.lastname: Heyman
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology*; D000818:Animals; D006332:Cardiomegaly / Q000473:pathology / Q000503:physiopathology; D002317:Cardiovascular Agents / Q000494:pharmacology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006333:Heart Failure / Q000150:complications / Q000473:pathology* / Q000503:physiopathology*; D000860:Hypoxia / Q000473:pathology / Q000503:physiopathology; D007213:Indomethacin / Q000494:pharmacology; D007679:Kidney Medulla / Q000473:pathology / Q000503:physiopathology; D007683:Kidney Tubular Necrosis, Acute / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D008138:Loop of Henle / Q000473:pathology / Q000503:physiopathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology; D014661:Vasoconstriction / Q000502:physiology; D014664:Vasodilation / Q000502:physiology
chemical_list: D002317:Cardiovascular Agents; D004791:Enzyme Inhibitors; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin