Iodixanol, constriction of medullary descending vasa recta, and risk for contrast medium-induced nephropathy.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
Institute of Vegetative Physiology, Charité-Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, Tucholskystrasse 2, Berlin 10117, Germany. mauricio.sendeski@charite.de
Mauricio
M
Sendeski
Andreas
A
Patzak
Thomas L
TL
Pallone
Chunhua
C
Cao
A Erik
AE
Persson
Pontus B
PB
Persson
D000704:Analysis of Variance; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D003287:Contrast Media / Q000494:pharmacology* / Q000633:toxicity*; D004730:Endothelium, Vascular / Q000187:drug effects; D007674:Kidney Diseases / Q000139:chemically induced*; D007679:Kidney Medulla / Q000098:blood supply* / Q000187:drug effects*; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects*; D012306:Risk; D014283:Triiodobenzoic Acids / Q000494:pharmacology* / Q000633:toxicity*; D014661:Vasoconstriction / Q000187:drug effects*
D003287:Contrast Media; D014283:Triiodobenzoic Acids; D000804:Angiotensin II; D009569:Nitric Oxide; C044834:iodixanol