Some aspects of sodium nitroprusside reaction with human erythrocytes.

Abstract

Sodium nitroprusside is an excellent agent for lowering blood pressure in hypertensive emergencies, for producing controlled hypotension during anesthesia, and for treating acute myocardial infarction and chronic heart failure. Toxic effects of this drug have been reported and above-normal cyanide and thiocyanate concentrations have been observed in the blood of a small proportion of subjects receiving nitroprusside. Nitrite, syanide, and thiocyanate are major decomposition products of nitroprusside, resulting from an in vitro reaction with human blood. On the basis of the conversion mechanism, we suggest that, in the cyanide/thiocyanate cycle, only cyanide is directly responsible for any acute toxicity attributed to sodium nitroprusside. In this work, the extent of cyanide production by erythrocytes in vitro was studied. The rate of detoxification of cyanide by human liver in vitro was experimentally determined and data from a search for a possible inhibitor of the nitroprusside/hemoglobin reaction are presented. Also, the possible mechanism of the nitroprusside/hemoglobin reaction is discussed.

Non-Heme Iron Nitrosyls in Biology

“…85 In an effort to understand this process an in vitro study suggested that when nitroprusside is mixed with erythrocytes there is rapid and complete conversion into iron ions, NO, and free cyanide. 86 This is a surprising reaction as the formation constants of cyanoferrates are very high; e.g., β 6 for hexacyanoferrate(II) is 10 36 . Butler et al 87 examined this claim with a nonintrusive analytical procedure using 90% 13 C-labeled nitroprusside.…”

“…There are reported deaths of patients while receiving nitroprusside . In an effort to understand this process an in vitro study suggested that when nitroprusside is mixed with erythrocytes there is rapid and complete conversion into iron ions, NO, and free cyanide . This is a surprising reaction as the formation constants of cyanoferrates are very high; e.g., β 6 for hexacyanoferrate(II) is 10 36 .…”

Desipramine induces eryptosis in human erythrocytes, an effect blunted by nitric oxide donor sodium nitroprusside and N-acetyl-L-cysteine but enhanced by Calcium depletion

“…Three aspects led us to speculate on the possible involvement of desipramine in the NO synthesis machinery of human erythrocytes: a) These cells possess nitric oxide synthase (NOS) [ 60–64 ], b) SNP favors their survival [ 68 ] and c) NOS antagonists reveal antidepressant-like properties [ 69–71 ]. To this end, we by-passed NOS-dependent NO generation by using slow releasing NO donor SNP [ 72–75 ]. Indeed pre-treatment of erythrocytes with SNP followed by addition of desipramine significantly blunted desipramine-induced eryptosis.…”

“…The fact that NO favors the survival of human erythrocytes [ 68 ], NOS antagonists possess anti-depressant properties [ 69–71 ] and the above mentioned publications led us to assume that desipramine might affect the NO synthesis machinery of human erythrocytes. Therefore, we by-passed NOS-dependent NO generation by using slow releasing NO donor SNP [ 72–75 ]. Indeed, pre-treatment of erythrocytes for 2 h with various concentrations of SNP (0.5, 1 and 1.5 µM) followed by the addition of desipramine (50 or 100 µM) significantly inhibited desipramine-induced eryptosis ( Figure 4 ).…”

Dosing-Time Dependent Effects of Sodium Nitroprusside on Cerebral, Renal, and Hepatic Catalase Activity in Mice

“…Indeed, it has been reported that, within minutes of infusion, SNP decomposes into metabolites that are pharmacologically inactive but toxicologically important [ 16 ]. Thus, one molecule of SNP is metabolized by combination with haemoglobin to produce one molecule of cyanmethaemoglobin and four CN ions [ 17 ]. Despite this, there have been few reported cases of CN − toxicity following the therapeutic administration of SNP [ 18 – 20 ].…”