Cyanide-induced increases in plasma catecholamines: relationship to acute toxicity

Cyanide is known to initiate release of catecholamines from chromaffin cells and isolated adrenals but the effect of cyanide on plasma catecholamine levels has not been reported. The present study demonstrates that cyanide produces marked elevation of plasma catecholamines in mice. A sublethal dose of KCN (5 mg/kg, sc) significantly increased plasma norepinephrine (NE) and epinephrine (EPI) at 5 min after administration, and the elevated levels returned to normal at 15 min. At a dose of 10 mg/kg, NE and EPI plasma levels remained elevated over a 15 min period. Multiple exposures to sublethal doses of KCN (5 mg/kg, sc, 4 doses at 15 min intervals) produced a steep, sustained rise in plasma NE and EPI. Administration of KCN (15.6 micrograms) directly into the lateral ventricles of the brain caused convulsions and respiratory depression, but did not affect plasma catecholamine levels. Pretreatment with pargyline did not alter the magnitude of the response to KCN. Adrenalectomy prevented the increase in plasma EPI and had no influence on plasma NE levels, indicating cyanide acts directly on the adrenals to stimulate EPI release. It is proposed that KCN directly stimulates the sympathoadrenal axis to increase plasma catecholamine levels.