S-Nitrosoproteins Functional Effects of Posttranslational Nitrosation

S-Nitrosoalbumin manifests a variety of novel effects that arise as a consequence of its S-nitrosation. In addition to its vasodilatory and platelet-inhibitory properties in vitro (Stamler et al., 1992c), administration of this 

NO adduct in vivo reduces mean blood pressure, enhances coronary blood flow, and prolongs bleeding time in dogs Kenney et al., 1993). Furthermore, in the Fobs model of cyclic coronary flow reduction, S-nitrosoalbumin reduces platelet-dependent coronary flow reductions in dogs when given at concentrations far below those that lead to reductions in mean blood pressure (Keaney et al., 1992). More recently, we showed that S-nitrosoalbumin is avid for subendothelial matrix, and that local delivery of NO through this mechanism limits smooth muscle proliferation following vascular injury (Marks et al., 1994). 

This work was supported in part by National Institutes of Health (NIH) grants HL-47416 and HL-48743, by a Merit Review Award from the U.S. Veterans Administration, and by a grant from NitroMed, Inc. G.R.U. is the recipient of a National Research Service Award from NIH (HL-09124) and an American College of Surgeons Fellowship Award. G.N.W. is the recipient of a Cardiovascular Training Grant Fellowship from NIH (T32 HL-07224). J.L. is the recipient of a Research Career Development Award from NIH (HL-02273). We express our appreciation to Stephanie Tribuna for expert technical assistance. 

Freedman, J. E., Welch, G., and Loscalzo, J. (1994). In vitro and in vivo transfer of nitric oxide from a low-molecular-weight S-nitrosothiol to albumin. Circulation 90, 1-354. Furchgott, R. F., and Zawadzki, J. F. (1980). The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature London) 288, 373-376. Gaston, B., Reilly, J., Drazen, J., Fackler, J., Ramdev, P., Mullins, M., Sugarbaker, D., Jaraki, 

Singel, D. J., Loscalzo, J., and Stamler, J. S. (1993). Endogenous nitrogen oxides and bronchodilator S-nitrosothiols in human airways. Proc. Natl. Acad. Sci. U.S.A. 90, 10957-10961. 

---