Iodinated contrast media inhibit oxygen consumption in freshly isolated proximal tubular cells from elderly humans and diabetic rats: Influence of nitric oxide

Per  Liss; Peter  Hansell; Angelica  Fasching; Fredrik  Palm

doi:10.3109/03009734.2016.1144664

Per Liss Department of Oncology, Radiology and Clinical Immunology, Section of Radiology, University Hospital, Uppsala, Sweden
Peter Hansell Department of Medical Cell Biology, Section of Integrative Physiology, Uppsala University, Uppsala, Sweden
Angelica Fasching Department of Medical Cell Biology, Section of Integrative Physiology, Uppsala University, Uppsala, Sweden
Fredrik Palm Department of Medical Cell Biology, Section of Integrative Physiology, Uppsala University, Uppsala, Sweden; and Department of Science and Health, Division of Drug Research, University of Linköping, Linköping, Sweden

DOI: https://doi.org/10.3109/03009734.2016.1144664

Keywords: Contrast media, human, nitric oxide, oxygen consumption, proximal tubule, rat

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.

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