In vitro degradation of nitroprusside in relation to in vivo decomposition and mechanism of action

Abstract The in vitro degradation of the vasodilator nitroprusside (200 ng/ml) was systematically studied in various media, viz. phosphate buffer (pH 7.4), albumin solution, cysteine and glutathione solutions, plasma, methaemoglobin and haemoglobin solutions, erythrocyte suspensions, whole blood and in 100,000 g crude aortic soluble fraction. Only in the aortic soluble fraction a fast decay of the nitroprusside concentration was observed. The extrapolated half-life time of about 2.6 min for the undiluted fraction approaches the in vivo half-life time as deduced from infusion experiments by other authors. Cyanide in a 100-fold excess over nitroprusside did not exert any effect on the rate of degradation in aortic soluble fraction. Probably the antagonizing effect of cyanide on the relaxation can be ascribed to a less efficient formation of nitrosyl-haeme from the prosthetic haeme-protein associated with guanylate cyclase and/or a direct effect on guanylate cyclase.