Iodixanol, Constriction of Medullary Descending Vasa Recta, and Risk for Contrast Medium–induced Nephropathy

Published Online:https://doi.org/10.1148/radiol.2513081732

Purpose: To determine whether a type of contrast medium (CM), iodixanol, modifies outer medullary descending vasa recta (DVR) vasoreactivity and nitric oxide (NO) production in isolated microperfused DVR.

Materials and Methods: Animal handling conformed to the Animal Care Committee Guidelines of all participating institutions. Single specimens of DVR were isolated from rats and perfused with a buffered solution containing iodixanol. A concentration of 23 mg of iodine per milliliter was chosen to mimic that expected to be used in usual examinations in humans. Luminal diameter was determined by using video microscopy, and NO was measured by using fluorescent techniques.

Results: Iodixanol led to 52% reduction of DVR luminal diameter, a narrowing that might interfere with passage of erythrocytes in vivo. Vasoconstriction induced by angiotensin II was enhanced by iodixanol. Moreover, iodixanol decreased NO bioavailability by more than 82%. Use of 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (a superoxide dismutase mimetic) prevented both vasoconstriction with iodixanol alone and increased constriction with angiotensin II caused by CM.

Conclusion: Iodixanol in doses typically used for coronary interventions constricts DVR, intensifies angiotensin II–induced constriction, and reduces bioavailability of NO. CM-induced nephropathy may be related to these events and scavenging of reactive oxygen species might exert a therapeutic benefit by preventing the adverse effects that a CM has on medullary perfusion.

Supplemental material: http://radiology.rsnajnls.org/cgi/content/full/2513081732/DC1

© RSNA, 2009

References

  • 1 Wysowski DK , Nourjah P. Deaths attributed to x-ray contrast media on U.S. death certificates. AJR Am J Roentgenol 2006; 186: 613–615. Crossref, MedlineGoogle Scholar
  • 2 Briguori C , Tavano D, Colombo A. Contrast agent–associated nephrotoxicity. Prog Cardiovasc Dis 2003; 45: 493–503. Crossref, MedlineGoogle Scholar
  • 3 Liss P , Persson PB, Hansell P, et al. Renal failure in 57 925 patients undergoing coronary procedures using iso-osmolar or low-osmolar contrast media. Kidney Int 2006; 70: 1811–1817. Crossref, MedlineGoogle Scholar
  • 4 Dangas G , Iakovou I, Nikolsky E, et al. Contrast-induced nephropathy after percutaneous coronary interventions in relation to chronic kidney disease and hemodynamic variables. Am J Cardiol 2005; 95: 13–19. Crossref, MedlineGoogle Scholar
  • 5 Schweiger MJ , Chambers CE, Davidson CJ, et al. Prevention of contrast induced nephropathy: recommendations for the high risk patient undergoing cardiovascular procedures. Catheter Cardiovasc Interv 2007; 69: 135–140. Crossref, MedlineGoogle Scholar
  • 6 Fishbane S . N-acetylcysteine in the prevention of contrast-induced nephropathy. Clin J Am Soc Nephrol 2008; 3: 281–287. Crossref, MedlineGoogle Scholar
  • 7 Stacul F , Adam A, Becker CR, et al. Strategies to reduce the risk of contrast-induced nephropathy. Am J Cardiol 2006; 98: 59K–77K. Crossref, MedlineGoogle Scholar
  • 8 Spargias K , Alexopoulos E, Kyrzopoulos S, et al. Ascorbic acid prevents contrast-mediated nephropathy in patients with renal dysfunction undergoing coronary angiography or intervention. Circulation 2004; 110: 2837–2842. Crossref, MedlineGoogle Scholar
  • 9 Tepel M , Aspelin P, Lameire N. Contrast-induced nephropathy: a clinical and evidence-based approach. Circulation 2006; 113: 1799–1806. Crossref, MedlineGoogle Scholar
  • 10 Marenzi G , Assanelli E, Marana I, et al. N-acetylcysteine and contrast-induced nephropathy in primary angioplasty. N Engl J Med 2006; 354: 2773–2782. Crossref, MedlineGoogle Scholar
  • 11 Heyman SN , Reichman J, Brezis M. Pathophysiology of radiocontrast nephropathy: a role for medullary hypoxia. Invest Radiol 1999; 34: 685–691. Crossref, MedlineGoogle Scholar
  • 12 Brezis M , Rosen S. Hypoxia of the renal medulla: its implications for disease. N Engl J Med 1995; 332: 647–655. Crossref, MedlineGoogle Scholar
  • 13 Pallone TL , Turner MR, Edwards A, et al. Countercurrent exchange in the renal medulla. Am J Physiol Regul Integr Comp Physiol 2003; 284: R1153–R1175. Crossref, MedlineGoogle Scholar
  • 14 Cowley AW Jr , Mori T, Mattson D, et al. Role of renal NO production in the regulation of medullary blood flow. Am J Physiol Regul Integr Comp Physiol 2003; 284: R1355–R1369. Crossref, MedlineGoogle Scholar
  • 15 Heyman SN , Brezis M, Reubinoff CA, et al. Acute renal failure with selective medullary injury in the rat. J Clin Invest 1988; 82: 401–412. Crossref, MedlineGoogle Scholar
  • 16 Herrera M , Ortiz PA, Garvin JL. Regulation of thick ascending limb transport: role of nitric oxide. Am J Physiol Renal Physiol 2006; 290: F1279–F1284. Crossref, MedlineGoogle Scholar
  • 17 Zhang Z , Rhinehart K, Solis G, et al. Chronic ANG II infusion increases NO generation by rat descending vasa recta. Am J Physiol Heart Circ Physiol 2005; 288: H29–H36. Crossref, MedlineGoogle Scholar
  • 18 Peti-Peterdi J , Warnock DG, Bell PD. Angiotensin II directly stimulates ENaC activity in the cortical collecting duct via AT(1) receptors. J Am Soc Nephrol 2002; 13: 1131–1135. Crossref, MedlineGoogle Scholar
  • 19 Mori T , O'Connor PM, Abe M, et al. Enhanced superoxide production in renal outer medulla of Dahl salt-sensitive rats reduces nitric oxide tubular-vascular cross-talk. Hypertension 2007; 49: 1336–1341. Crossref, MedlineGoogle Scholar
  • 20 Pallone TL , Work J, Myers RL, et al. Transport of sodium and urea in outer medullary descending vasa recta. J Clin Invest 1994; 93: 212–222. Crossref, MedlineGoogle Scholar
  • 21 Kojima H , Nakatsubo N, Kikuchi K, et al. Detection and imaging of nitric oxide with novel fluorescent indicators: diaminofluoresceins. Anal Chem 1998; 70: 2446–2453. Crossref, MedlineGoogle Scholar
  • 22 Zhang Z , Pallone TL. Response of descending vasa recta to luminal pressure. Am J Physiol Renal Physiol 2004; 287: F535–F542. Crossref, MedlineGoogle Scholar
  • 23 Brunner E , Puri M. Nonparametric methods in factorial designs. Stat Papers 2001; 42: 1–52. CrossrefGoogle Scholar
  • 24 Brezis M , Epstein FH. A closer look at radiocontrast-induced nephropathy. N Engl J Med 1989; 320: 179–181. Crossref, MedlineGoogle Scholar
  • 25 Mattson DL . Importance of the renal medullary circulation in the control of sodium excretion and blood pressure. Am J Physiol Regul Integr Comp Physiol 2003; 284: R13–R27. Crossref, MedlineGoogle Scholar
  • 26 Park F , Mattson DL, Roberts LA, et al. Evidence for the presence of smooth muscle alpha-actin within pericytes of the renal medulla. Am J Physiol 1997; 273: R1742–R1748. MedlineGoogle Scholar
  • 27 Heyman SN , Brezis M, Epstein FH, et al. Early renal medullary hypoxic injury from radiocontrast and indomethacin. Kidney Int 1991; 40: 632–642. Crossref, MedlineGoogle Scholar
  • 28 Liss P , Nygren A, Olsson U, et al. Effects of contrast media and mannitol on renal medullary blood flow and red cell aggregation in the rat kidney. Kidney Int 1996; 49: 1268–1275. Crossref, MedlineGoogle Scholar
  • 29 Liss P , Nygren A, Hansell P. Hypoperfusion in the renal outer medulla after injection of contrast media in rats. Acta Radiol 1999; 40: 521–527. Crossref, MedlineGoogle Scholar
  • 30 Seeliger E , Flemming B, Wronski T, et al. Viscosity of contrast media perturbs renal hemodynamics. J Am Soc Nephrol 2007; 18: 2912–2920. Crossref, MedlineGoogle Scholar
  • 31 Lancelot E , Idee JM, Couturier V, et al. Influence of the viscosity of iodixanol on medullary and cortical blood flow in the rat kidney: a potential cause of nephrotoxicity. J Appl Toxicol 1999; 19: 341–346. Crossref, MedlineGoogle Scholar
  • 32 Navar LG , Nishiyama A. Why are angiotensin concentrations so high in the kidney? Curr Opin Nephrol Hypertens 2004; 13: 107–115. Crossref, MedlineGoogle Scholar
  • 33 Prieto-Carrasquero MC , Botros FT, Pagan J, et al. Collecting duct renin is upregulated in both kidneys of 2-kidney, 1-clip goldblatt hypertensive rats. Hypertension 2008; 51: 1590–1596. Crossref, MedlineGoogle Scholar
  • 34 Agmon Y , Peleg H, Greenfeld Z, et al. Nitric oxide and prostanoids protect the renal outer medulla from radiocontrast toxicity in the rat. J Clin Invest 1994; 94: 1069–1075. Crossref, MedlineGoogle Scholar
  • 35 Mori T , Cowley AW Jr. Angiotensin II-NAD(P)H oxidase-stimulated superoxide modifies tubulovascular nitric oxide cross-talk in renal outer medulla. Hypertension 2003; 42: 588–593. Crossref, MedlineGoogle Scholar
  • 36 Zhang Z , Rhinehart K, Kwon W, et al. ANG II signaling in vasa recta pericytes by PKC and reactive oxygen species. Am J Physiol Heart Circ Physiol 2004; 287: H773–H781. Crossref, MedlineGoogle Scholar
  • 37 Merten GJ , Burgess WP, Gray LV, et al. Prevention of contrast-induced nephropathy with sodium bicarbonate: a randomized controlled trial. JAMA 2004; 291: 2328–2334. Crossref, MedlineGoogle Scholar
  • 38 Tepel M , van der GM, Schwarzfeld C, et al. Prevention of radiographic-contrast-agent-induced reductions in renal function by acetylcysteine. N Engl J Med 2000; 343: 180–184. Crossref, MedlineGoogle Scholar

Article History

Published in print: 2009