Nitroprusside: A Potpourri of Biologically Reactive Intermediates

  • Roger P. Smith
  • Dean E. Wilcox
  • Harriet Kruszyna
  • Robert Kruszyna
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 283)


Sodium nitroprusside, Na2[Fe(CN)5NO], (SNP) has been recognized as a potent, directly acting vasodilator for over a half-century. More recently, it has been found also to inhibit blood platelet aggregation and adhesion. These biologicial activities are ascribed to the nitrosyl ligand on SNP which is thought to activate guanylate cyclase by binding to its critical heme group. c-GMP in turn initiates a cascade of kinase reactions which result in the utimate biological effects. Thus, SNP is one of the compounds known as the nitric oxide (NO) vasodilators (Ignarro, 1989) which mimic the effects of the so-called endothelium-derived relaxing factor (Furchgott and Zawadzki, 1980), an endogenous mediator which many are convinced is identical to NO. The same or a similar factor is believed to play in role in excitatory amino acid transmission in the central nervous system, and to be the cytotoxic factor synthesized by neutrophils and macrophages (Collier and Valiance, 1989).


Nitric Oxide Electron Paramagnetic Resonance Methylene Blue Sodium Nitroprusside Guanylate Cyclase 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Brune, B., and Lapetina, E. G. (1989). Activation of a cytosolic ADP-ribosyl-transferase by nitric oxide-generating agents. J. Biol. Chem. 264, 8455–8458.PubMedGoogle Scholar
  2. Butler, A. R., and Glidewell, C. (1987). Recent chemical studies of sodium nitroprusside relevant to its hypotensive action. Chem. Soc. Rev. 16, 361–380.CrossRefGoogle Scholar
  3. Collier, J., and Valiance, P. (1989). Second messenger role for NO widens to nervous and immune systems. TIPS 10, 427–431.PubMedGoogle Scholar
  4. Devlin, D. J., Smith, R. P., and Thron, C. D. (1989). Cyanide release from nitroprusside in the isolated, perfused, bloodless liver and hindlimbs of the rat. Toxicol. Appi. Pharmacol. 99, 354–356.CrossRefGoogle Scholar
  5. Furchgott, R. F., and Zawadski, J. V. (1980). The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 288, 373–376.CrossRefPubMedGoogle Scholar
  6. Furchgott, R. F., and Vanhoutte, P. M. (1989). Endothelium-derived relaxing and contracting factors. FASEB J. 3, 2007–2018.Google Scholar
  7. Ignarro, L. J. (1989). Heme-dependent activation of soluble guanylate cyclase by nitric oxide: Regulation of enzyme activity by porphyrins and metalloporphyrins. Semin. Hematol. 26, 63–76.PubMedGoogle Scholar
  8. Kruszyna, H., Kruszyna, R., and Smith, R. P. (1982). Nitroprusside increases guanylate monophosphate concentrations during the relaxation of rabbit aortic strips and both effects are antagonized by cyanide. Anesthesiology 57, 303–308.CrossRefPubMedGoogle Scholar
  9. Kruszyna, H., Kruszyna, R., and Smith, R. P. (1985). Cyanide and sulfide interact with nitrogenous compounds to influence the relaxation of various smooth muscles. Proc. Soc. Exp. Biol. Med. 179, 44–49.Google Scholar
  10. Kruszyna, H., Kruszyna, R., Smith, R. P., and Wilcox, D. E. (1987). Red blood cells generate nitric oxide from directly acting nitrogenous vasodilators. Toxicol. Appt. Pharmacol. 91, 429–438.CrossRefGoogle Scholar
  11. Kruszyna, R., Kruszyna, H., Smith, R. P., Thron, C. D., and Wilcox, D. E. (1987). Nitrite conversion to nitric oxide in red cells and its stabilization as a nitrosylated valency hybrid of hemoglobin. J. Pharmacol. Exp. Ther. 241, 307–313.PubMedGoogle Scholar
  12. Kruszyna, R., Kruszyna, H., Smith, R. P., and Wilcox, D. E. (1988). Generation of valency hybrid species of hemoglobin in mice by nitric oxide vasodilators. Toxicol. Appl. Pharmacol. 94, 458–465.CrossRefPubMedGoogle Scholar
  13. Schwerin, F. T., Rosenstein, R., and Smith, R. P. (1983). Cyanide prevents the inhibition of platelet aggregation by nitroprusside, hydroxylamine and azide. Thromb. Haemostas. 50, 780–783.Google Scholar
  14. Shafer, P. R., Wilcox, D. E., Kruszyna, H., Kruszyna, R., and Smith, R. P. (1989). Decomposition and specific exchange of the trans-cyanide ligand on nitroprusside is facilitated by hemoglobin. Toxicol. Appl. Pharmacol. 99, 1–10.CrossRefPubMedGoogle Scholar
  15. Smith, R. P., and Kruszyna, H. (1974). Nitroprusside produces cyanide poisoning via a reaction with hemoglobin. J. Pharmacol. Exp. Ther. 191, 557–563.PubMedGoogle Scholar
  16. Wilcox, D. E., Kruszyna, H., Kruszyna, R., and Smith, R. P. (1990). Effect of cyanide on the reaction of nitroprusside with hemoglobin: Relevance to cyanide interference with the biological activity of nitroprusside. Chem. Res. Toxicol. In press.Google Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Roger P. Smith
    • 1
  • Dean E. Wilcox
    • 2
  • Harriet Kruszyna
    • 1
  • Robert Kruszyna
    • 1
  1. 1.Department of Pharmacology and ToxicologyDartmouth Medical School and Dartmouth CollegeHanoverUSA
  2. 2.Department of ChemistryDartmouth Medical School and Dartmouth CollegeHanoverUSA

Personalised recommendations