Ignarro

Three years later Robert F Furchgott discov ered that the relaxing of smooth muscles such as blood vessel walls was stimulated by an unknown substance produced in the lining of the blood vessels (the endothelium) He called this substance the endothelium-dependent relaxing factor or EDRF and in 1986 showed that EDRF was NO Louis J Ignarro reached the same conclusion at about the same time Further support was provided by Salvador Moncada who showed that endothelial cells did in deed produce NO and that the l arginine to l citrulline conversion was responsible... 

Kleinert H, Boissel J-P, Schwarz PM et al (2000) Regulation of the expression of nitric oxide synthases. In Ignarro LJ (ed) Nitric oxide, biology and pathobiology. Academic Press, San Diego, CA, pp 105-128... 

Ignarro, L.J. (1990). Biosynthesis and metabolism of endothelium-derived relaxation factor. Ann. Rev. Pharmacol. Toxicol. 30, 535-560. 

When Murad, Furchgott, and Ignarro received their Nobel Prizes, however, scientists still did not know exactly how nitroglycerin was broken down by the body and converted into nitric oxide. In 2002, researchers at Duke University in North Carolina found an enzyme in mitochondria, the cell s powerhouse, that they believe is responsible for this process. This discovery also explained a phenomenon that doctors had long observed—over time, nitroglycerin stops working and no longer relieves the patient s chest pain. 

L.J. Ignarro, G.M. Buga, K.S. Wood, R.E. Byrns, and G. Chaudhuri, Endothelium-derived relaxing factor produced and released from artery and vein is nitric-oxide. Proc. Natl. Acad. Sci. U.S.A. 84, 9265-9269 (1987). 

L.J. Ignarro, Nitric-Oxide - A novel signal transduction mechanism for transcellular communication. 

LJ Ignarro, GM Buga, KS Wood, RE Byrn, G Chaudhuri. Proc Natl Acad Sci USA 84 9265-9269, 1987. 

Nitric Oxide Biology and Pathobiology Eds. Ignarro, L. J.2000. Academic Press San Diego, 2000. 

McMahon, T. J., Gow, A., Stamler, J. A. Nitric Oxide Biology and Pathobiology, Chapter 15 Ed. Ignarro, L.J. Academic Press San Diego, 2000, and references therein. 

R11 —SNO), which upregulates sGC, leading to increase in cGMP and relaxation. In the course oftheir interaction with organic nitrate, thiols (R1—SH) are oxidised to disulfides (R1—S—S—R1). Adapted from Ignarro et ai. [11]. 

The extent to which nitrite can serve as a physiological source of NO has been extensively discussed. As noted above, Ignarro and colleagues proposed that nitrite is an intermediate in the bioconversion of GTN to NO (Scheme 2.1). However, nitrite has been shown to be 1000-fold less effective than GTN in the stimulation of sGC [50]. While this difference could be attributed to the inability of hydrophilic nitrite to cross cell membranes, levels of intracellular and plasma concentrations of nitrite have been... 

It is worth noting that S-nitrosothiols, originally implicated by Ignarro and colleagues in the bioactivation of organic nitrates (Scheme 2.1), have been shown to be reduced to NO in the presence of XOR [94]. 

Ignarro, L. J., Gruetter, C. A., Requirement of thiols for activation of coronary arterial guanylate cyclase by glycerol trinitrate and sodium nitrite Possible involvement of S-nitrosothiols. Biochim. Biophys. 

Ignarro, L. J., After 130 years, the molecular mechanism of action of nitroglycerin is revealed. Proc. Natl. Acad. Sci. USA 99 (2002),... 

Rogers, N. E., Ignarro, L. J., Constitutive nitric oxide synthase from cerebellum is reversibly inhibited by nitric oxide formed from L-arginine, Biochem. Biophys. Res. Commun. 189 (1992), p. 242—249... 

---