title: Nitric oxide and prostanoids protect the renal outer medulla from radiocontrast toxicity in the rat.
abstract: Human radiocontrast nephrotoxicity is predicted by the presence of multiple risk factors, often associated with compromised renal circulation. To produce a simple model of radiocontrast nephropathy, rats were pretreated with indomethacin and N omega-nitro-L-arginine methyl ester (L-NAME, to inhibit nitric oxide synthesis) before the administration of iothalamate. Acute renal failure consistently developed, with a decline in creatinine clearance from 1.05 +/- 0.10 to 0.27 +/- 0.05 ml/min (P < 0.001) associated with selective necrosis of 49 +/- 9% of medullary thick ascending limbs. Hemodynamic studies using laser-Doppler probes revealed that when injected alone, iothalamate increased outer medullary blood flow to 196 +/- 25% of baseline (P < 0.001). Pretreatment by L-NAME or indomethacin both reduced basal medullary blood flow and transformed the medullary vasodilator response to radiocontrast into vasoconstriction, with a prolonged reduction of medullary blood flow to less then half of baseline. Combined administration of indomethacin, L-NAME, and iothalamate lowered medullary blood flow to 12 +/- 4% of baseline. We conclude that prostanoids and nitric oxide have an important protective role in the renal response to radiocontrast material. Reduced synthesis of these vasoactive substances in renal/vascular diseases may predispose patients to radiocontrast nephropathy.
authors.affiliation: Department of Medicine, Hadassah University Hospital, Mount-Scopus, Jerusalem, Israel.
authors.forename: Y
authors.initials: Y
authors.lastname: Agmon
authors.forename: H
authors.initials: H
authors.lastname: Peleg
authors.forename: Z
authors.initials: Z
authors.lastname: Greenfeld
authors.forename: S
authors.initials: S
authors.lastname: Rosen
authors.forename: M
authors.initials: M
authors.lastname: Brezis
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000517:prevention & control; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D007483:Iothalamic Acid / Q000633:toxicity*; D007672:Kidney Cortex / Q000187:drug effects / Q000473:pathology; D007679:Kidney Medulla / Q000098:blood supply* / Q000187:drug effects / Q000473:pathology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000502:physiology*; D011453:Prostaglandins / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D011453:Prostaglandins; D007483:Iothalamic Acid; D009569:Nitric Oxide; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin