Toxicology of some inorganic antihypertensive anions.
Sodium nitroprusside reacts with hemoglobin in vitro and in vivo to cause the formation of cyanmethemoglobin and the liberation of excess free cyanide. The latter is responsible for the typical signs of acute cyanide poisoning in mice after lethal doses of nitroprusside. Differences in the reactivity of the red cells of various species toward nitroprusside are due to differences in the permeability of the red cell membranes to nitropruside. In vivo thiocyanate results in the formation of methemoglobin in an elevation of blood cyanide levels in mice. The latter, however, does not result in cyanide poisoning since it is bound in the biologically inert form of cyanmethemoglobin. Thus, both nitroprusside and thiocyanate generate their own antidote in mice, but an excess of cyanide is released in the case of nitroprusside whereas excess methemoglobin is generated in the case of thiocyanate. Acute poisoning with thiocyanate salts apparently involves direct excitatory effects on the central nervous system. In vitro the reaction between thiocyanate and hemoglobin proceeds only in the presence of hydrogen peroxide. Chronic administration of nitroprusside results in the elevation of blood thiocyanate levels presumably because of continuous, endogenous cyanide metabolism via rhodanese (thiosulfate sulfurtransferase). When one includes these previously unrecognized effects of nitroprusside and thiocyanate, there appears to be some correlation between the ability of a chemical to oxidize hemoglobin and its ability to activate nonadrenergic receptors for the relaxation of vascular smooth muscle.
D000818:Animals; D000959:Antihypertensive Agents / Q000633:toxicity*; D055598:Chemical Phenomena; D002621:Chemistry; D003486:Cyanides / Q000037:antagonists & inhibitors / Q000097:blood / Q000633:toxicity; D005260:Female; D005292:Ferricyanides / Q000633:toxicity*; D006454:Hemoglobins; D051379:Mice; D008954:Models, Biological; D009573:Nitrites / Q000633:toxicity*; D009599:Nitroprusside / Q000633:toxicity*; D013861:Thiocyanates / Q000633:toxicity*; D014666:Vasomotor System / Q000187:drug effects
D000959:Antihypertensive Agents; D003486:Cyanides; D005292:Ferricyanides; D006454:Hemoglobins; D009573:Nitrites; D013861:Thiocyanates; D009599:Nitroprusside