A ROLE FOR NITRIC-OXIDE IN X-RAY CONTRAST MATERIAL TOXICITY

Rationale and Objectives. We assessed the role that nitric oxide (NO) plays in contrast media (CM) toxicity, using 100% lethal dose (LD(100) ) studies in hyperimmune Brown Norway (BN) rats. Methods. Ninety-two B N rats and 41 Sprague-Dawley (SD) rats underwent CM LD(100) tail vein injections with methylglucamine iothalamate or sodium iothalamate to t he point of cessation of respiration. Methylglucamine hydrochloride al so nas injected. The injections were accompanied by L-arginine (L-Arg) or D-arginine (D-Arg) analogues or by an H-1 blocker. L-Arg analogues inhibit NO formation, and D-Arg analogues do not. Results. An L-Arg a nalogue, but not a D-Arg analogue, increased the tolerance of BN rats (p < .005) for methylglucamine iothalamate but not for sodium iothalam ate. The L-Arg analogue also protected BN rats against methylglucamine chloride injections (p < .002). H-1 blockade protected BN rats agains t methylglucamine iothalamate (p < .0005) and methylglucamine chloride (p < .005) injections. None of these measures altered the CM toleranc e of SD rats. In SD rats, injections of either methylglucamine iothala mate or sodium iothalamate along with a D-Arg analogue or normal salin e were better tolerated than similar injections in BN rats (p < .01 an d .002 for methylglucamine iothalamate and sodium iothalamate: respect ively). In SD rats but not BN rats, sodium iothalamate was better tole rated than was methylglucamine iothalamate (p < .0005). Conclusion. NO appears to play a significant role in BN rats' LD(100) CM toxicity an d has been implicated by others in the blood pressure fall characteriz ing some forms of antigen-induced anaphylaxis [1, 2]. The results of t he current study and the literature suggest that methylglucamine-modul ated release of histamine from mast cells may underlie the NO producti on.