1 Since the literature suggested a portion of the overall toxicity of cyanide (CN) may be affected by nitric oxide, we investigated a long acting NO releasing complex (diethy lamine/nitric oxide (DEA/NO)) which may exhibit vasodi latory as well as other nitric oxide effects to determine its ability to modify CN toxicity. Sodium nitrite, a vasodilator commonly used to treat cyanide toxicity thought to act by methemoglobin (MHb) formation, can be rapidly trans formed to nitric oxide (NO).

2 Mice (n=10 per dose) were administered one of five doses of sodium cyanide (NaCN) intraperitoneally (4.28,5.08,6.03,7.17 and 8.52 mg kg^-1). DEA/NO was given intravenously (20 mg kg^-1) 2 min prior to NaCN. As a control, N^G-monomethyl-L-arginine (L-NMMA), which inhibits NO synthesis, was administered intravenously (70 mg kg^-1) to mice, 3 min prior to DEA/NO.

3 Before CN toxicity studies, we determined whether DEA/NO was producing MHb by collecting tail vein blood from mice and measuring MHb levels. For example, 4 min after DEA/NO administration (5,10, and 20 mg kg^-1), MHb levels were 1.2 7 ± 0.28%, 2.60 ± 0.26% and 6.53 ±0.54% respectively. O₂ capacity was also decreased in a dose related manner. Carboxyhemoglobin or percent O₂ satura tion, on the other hand, was not significantly inhibited. The LD₅₀ increased from 5.75 ± 0.026 (CN alone) to 7.66 ± 0.021 mg kg^-1 (CN+DEA/NO) resulting in a protec tive ratio of 1.73.

4 Results suggest the following: (1) L-NMMA, which inhibits the synthesis of endogenous NO, appears to exacerbate the DEA/NO (or exogenous NO) response; (2) DEA/NO appears to reduce the toxicity of CN which suggests that a portion of CN toxicity may be affected by a NO component; and (3) low DEA/NO doses may act via a direct effect while higher doses (40 mg kg^-1) may allow for formation of a concentration of MHb which can bind CN to form cyanomethemoglobin and reduce the toxicity of CN.