title: Iodinated contrast media inhibit oxygen consumption in freshly isolated proximal tubular cells from elderly humans and diabetic rats: Influence of nitric oxide.
abstract: Objectives Mechanisms underlying contrast medium (CM)-induced nephropathy remain elusive, but recent attention has been directed to oxygen availability. The purpose of this study was to evaluate the effect of the low-osmolar CM iopromide and the iso-osmolar CM iodixanol on oxygen consumption (QO2) in freshly isolated proximal tubular cells (PTC) from kidneys ablated from elderly humans undergoing nephrectomy for renal carcinomas and from normoglycemic or streptozotocin-diabetic rats. Materials PTC were isolated from human kidneys, or kidneys of normoglycemic or streptozotocin-diabetic rats. QO2 was measured with Clark-type microelectrodes in a gas-tight chamber with and without each CM (10 mg I/mL medium). L-NAME was used to inhibit nitric oxide (NO) production caused by nitric oxide synthase. Results Both CM reduced QO2 in human PTC (about -35%) which was prevented by L-NAME. PTC from normoglycemic rats were unaffected by iopromide, whereas iodixanol decreased QO2 (-34%). Both CM decreased QO2 in PTC from diabetic rats (-38% and -36%, respectively). L-NAME only prevented the effect of iopromide in the diabetic rat PTC. Conclusions These observations demonstrate that CM can induce NO release from isolated PTC in vitro, which affects QO2. Our results suggest that the induction of NO release and subsequent effect on the cellular oxygen metabolism are dependent on several factors, including CM type and pre-existing risk factors for the development of CM-induced nephropathy.
authors.affiliation: a Department of Oncology, Radiology and Clinical Immunology, Section of Radiology , University Hospital , Uppsala , Sweden ;
authors.forename: Per
authors.initials: P
authors.lastname: Liss
authors.affiliation: b Department of Medical Cell Biology, Section of Integrative Physiology , Uppsala University , Uppsala , Sweden ;
authors.forename: Peter
authors.initials: P
authors.lastname: Hansell
authors.affiliation: b Department of Medical Cell Biology, Section of Integrative Physiology , Uppsala University , Uppsala , Sweden ;
authors.forename: Angelica
authors.initials: A
authors.lastname: Fasching
authors.affiliation: b Department of Medical Cell Biology, Section of Integrative Physiology , Uppsala University , Uppsala , Sweden ;|c Department of Science and Health, Division of Drug Research , University of Linköping , Linköping , Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Palm
mesh_terms: D000368:Aged; D000818:Animals; D003287:Contrast Media / Q000633:toxicity*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D010101:Oxygen Consumption / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D003287:Contrast Media; D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester
keywords: Contrast media; human; nitric oxide; oxygen consumption; proximal tubule; rat