A role for nitric oxide in X-ray contrast material toxicity.
OBJECTIVE
We assessed the role that nitric oxide (NO) plays in contrast media (CM) toxicity, using 100% lethal dose (LD100) studies in hyperimmune Brown Norway (BN) rats.


METHODS
Ninety-two BN rats and 41 Sprague-Dawley (SD) rats underwent CM LD100 tail vein injections with methylglucamine iothalamate or sodium iothalamate to the point of cessation of respiration. Methylglucamine hydrochloride also was injected. The injections were accompanied by L-arginine (L-Arg) or D-arginine (D-Arg) analogues or by an H1 blocker. L-Arg analogues inhibit NO formation, and D-Arg analogues do not.


RESULTS
An L-Arg analogue, but not a D-Arg analogue, increased the tolerance of BN rats (p < .005) for methylglucamine iothalamate but not for sodium iothalamate. The L-Arg analogue also protected BN rats against methylglucamine chloride injections (p < .002). H1 blockade protected BN rats against methylglucamine iothalamate (p < .0005) and methylglucamine chloride (p < .005) injections. None of these measures altered the CM tolerance of SD rats. In SD rats, injections of either methylglucamine iothalamate or sodium iothalamate along with a D-Arg analogue or normal saline were better tolerated than similar injections in BN rats (p < .01 and .002 for methylglucamine iothalamate and sodium iothalamate, respectively). In SD rats but not BN rats, sodium iothalamate was better tolerated than was methylglucamine iothalamate (p < .0005).


CONCLUSIONS
NO appears to play a significant role in BN rats LD100 CM toxicity and has been implicated by others in the blood pressure fall characterizing some forms of antigen-induced anaphylaxis [1, 2]. The results of the current study and the literature suggest that methylglucamine-modulated release of histamine from mast cells may underlie the NO production.
Lasser
E C
EC
Department of Radiology, University of California, San Diego, La Jolla 92093-0632, USA.
Lamkin
G E
GE
Lyon
S
S
D000707:Anaphylaxis / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D003287:Contrast Media / Q000008:administration & dosage / Q000633:toxicity*; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D007275:Injections, Intravenous; D007482:Iothalamate Meglumine / Q000008:administration & dosage / Q000633:toxicity; D007483:Iothalamic Acid / Q000008:administration & dosage / Q000633:toxicity; D008168:Lung / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D011914:Rats, Inbred BN; D017207:Rats, Sprague-Dawley; D019323:omega-N-Methylarginine / Q000494:pharmacology
D003287:Contrast Media; D004791:Enzyme Inhibitors; D006634:Histamine H1 Antagonists; D007483:Iothalamic Acid; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester; D007482:Iothalamate Meglumine