title: Failure of cyanide to antagonize sodium nitroprusside in vivo in dogs.
abstract: The role of cyanide (CN) in the mechanism of action of sodium nitroprusside (SNP) has not been well defined. Some authors consider accumulation of CN in muscle to be the principal factor responsible for resistance to SNP when given to induce hypotension. To test this hypothesis, SNP was infused in 12 anesthetized dogs. Mean aortic blood pressure was reduced 50% and dogs were maintained at this pressure for 5 minutes. After recovery, eight of the dogs (group 1) received a potassium cyanide (KCN) infusion at a rate of 0.0125 mg/kg/min for 180 minutes; the other four dogs (group 2) were given saline solution and served as controls. After 180 minutes, all 12 dogs received a second infusion of SNP in the same dose as their first. No significant differences in blood pressure or heart rate were observed between groups. Left ventricular end-diastolic pressure (LVEDP) and dP/dt were elevated following KCN; however, after the second SNP infusion these parameters decreased in both groups. Cardiac output (Qt) decreased to 55% of baseline during the first SNP infusion and showed no significant changes during the second SNP infusion, but total peripheal resistance decreased significantly during both SNP infusions. Although whole-blood CN levels and gracilis muscle tissue CN concentrations were significantly greater (p < 0.05) in group 1 after KCN, the cardiovascular effects of SNP were not significantly altered by these increases in KCN, the cardiovascular effects of SNP were not significantly altered by these increases in CN. The authors conclude that resistance to SNP in induced hypotension is not the result of direct effects of CN on smooth muscle.
mesh_terms: D000818:Animals; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects*; D002302:Cardiac Output / Q000187:drug effects; D003486:Cyanides / Q000097:blood / Q000494:pharmacology*; D004285:Dogs; D005292:Ferricyanides / Q000037:antagonists & inhibitors*; D006339:Heart Rate / Q000187:drug effects; D009599:Nitroprusside / Q000037:antagonists & inhibitors*; D013618:Tachyphylaxis
chemical_list: D003486:Cyanides; D005292:Ferricyanides; D009599:Nitroprusside