title: Iodinated contrast media differentially affect afferent and efferent arteriolar tone and reactivity in mice: a possible explanation for reduced glomerular filtration rate.
abstract: OBJECTIVE
  To determine the effect of the iodinated contrast medium iodixanol on arteriolar tone in afferent and efferent arterioles of the glomerulus and the functional interactions with the major modulators of arteriolar tone, angiotensin II and nitric oxide, in mice.
  
  
  METHODS
  Animal handling conformed to the ethics guidelines of the Office for Health and Social Matters of Berlin. Arterioles were isolated from 136 C57BL/6 mice, perfused with either vehicle solution or iodixanol (23 mg of iodine per milliliter) for 20 minutes, followed by angiotensin II administration. Fluorescence of 3-amino-4-(N-methylamino)-2',7'-difluorofluorescein (DAF-FM) and dihydroethidium (DHE) were used for quantification of nitric oxide bioavailability and superoxide concentration, respectively. Statistical analysis of time- and dose-dependent data was performed by using the nonparametric test for repeated measurements.
  
  
  RESULTS
  With iodixanol, afferent arteriole diameters were significantly reduced from 9.2 µm to 8.3 µm; in control group, the diameters were increased from 8.7 µm to 9.3 µm (P = .008). Nitric oxide synthase inhibition augmented iodixanol-induced constriction, with diameters reduced from 9.9 µm to 5.8 µm (P < .0001). DAF-FM fluorescence increased less during iodixanol treatment and nitric oxide synthase inhibition (3.6% and 3.7% vs 10.7% in control group, P = .009 and P = .049, respectively), indicating impaired nitric oxide bioavailability. With iodixanol, DHE fluorescence ratio was increased by 12% (P < .0001). Angiotensin II responses were enhanced by iodixanol and by nitric oxide synthase inhibition after perfusion with iodixanol (3.3 µm and 4.3 µm vs 7.5 µm [control group] with 1 × 10(-6)/mol/L angiotensin II, P = .03 for both). In contrast, in efferent arterioles, neither their basal diameters nor the responses to angiotensin II were significantly affected by iodixanol.
  
  
  CONCLUSIONS
  A more pronounced effect of iodixanol on afferent than on efferent arterioles may contribute to the reduction of glomerular filtration rate in contrast medium-induced acute kidney injury. Decreased nitric oxide bioavailability and increased concentration of superoxide explain the increased tone and reactivity in afferent arterioles perfused with iodixanol.
authors.affiliation: Institute of Vegetative Physiology, Charité-Universitätsmedizin Berlin, Hessische Strasse 3-4, 10115 Berlin, Germany.
authors.forename: Zhi Z
authors.initials: ZZ
authors.lastname: Liu
authors.forename: Vinicius U
authors.initials: VU
authors.lastname: Viegas
authors.forename: Andrea
authors.initials: A
authors.lastname: Perlewitz
authors.forename: En Y
authors.initials: EY
authors.lastname: Lai
authors.forename: Pontus B
authors.initials: PB
authors.lastname: Persson
authors.forename: Andreas
authors.initials: A
authors.lastname: Patzak
authors.forename: Mauricio M
authors.initials: MM
authors.lastname: Sendeski
mesh_terms: D000704:Analysis of Variance; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000187:drug effects*; D003287:Contrast Media / Q000494:pharmacology*; D003497:Cyclic N-Oxides / Q000494:pharmacology; D003997:Dicarbethoxydihydrocollidine / Q000031:analogs & derivatives / Q000494:pharmacology; D005021:Ethylamines / Q000494:pharmacology; D005452:Fluoresceins / Q000494:pharmacology; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D007678:Kidney Glomerulus / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D013113:Spin Labels; D018709:Statistics, Nonparametric; D013481:Superoxides / Q000378:metabolism; D014283:Triiodobenzoic Acids / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: C527813:3-amino-4-monomethylamino-2',7'-difluorofluorecein; D003287:Contrast Media; D003497:Cyclic N-Oxides; D005021:Ethylamines; D005452:Fluoresceins; D013113:Spin Labels; D014283:Triiodobenzoic Acids; C514241:dihydroethidine; D013481:Superoxides; D000804:Angiotensin II; D009569:Nitric Oxide; D003997:Dicarbethoxydihydrocollidine; C044834:iodixanol; C001803:tempol; D019331:NG-Nitroarginine Methyl Ester