Nitric oxide and S-nitrosothiols in human blood

The hypothesis that endothelial-derived relaxing factor (EDRF) is nitric oxide has stimulated a wealth of research into the significance of this novel intriguing molecule. Given its short life, many storage forms of NO as well as targets have been postulated. Among these, a pool of derivatives of NO (S-nitrosothiols, RSNOs) covalently bound to SH groups of proteins and low molecular weight thiols (e.g., glutathione) have been identified in various biological systems. The importance of RSNOs results from the very similar biological actions exhibited by both NO and RSNOs in vivo as well as in vitro. In particular, it has been observed that in the bloodstream, these molecules are able to provoke vasodilatation with a consequent fall in blood pressure and an antithrombotic effect by inhibition of platelet aggregation. Many hypotheses have been postulated about the biochemical species and the mechanisms involved in these processes, but many aspects have not yet been clarified. In addition, some RSNOs have been recently proposed to be clinical parameters, whose levels may vary under some pathological conditions. The therapeutic utility of RSNOs as an alternative to classic NO donors has also been suggested. Here, we provide a critical analysis of the main reports about the biochemical, physiological, pathological and therapeutic properties of RSNOs in the cardiovascular system. Particular attention is addressed to conflicting results and to discrepancies in the methodologies and models utilized. The numerous unanswered questions concerning the role of RSNOs in the control of vascular tone are discussed.