Fates and vascular action of S-nitrosoglutathione and related compounds inthe circulation

To know the metabolism of low-molecular-weight S-nitrosothiols (RS-NO) in t he circulation, we analyzed the stability and depressor effects of S-nitros oglutathione (GS-NO) and the L- and D-forms of S-nitrosocysteine (Cys-NO). Although half-lives of these RS-NO in fresh plasma were longer than 50 min, their depressor effects disappeared within 5 min after intravenous adminis tration of these compounds. Acivicin (AT-125), an inhibitor of gamma-glutam yltransferase (gamma-GTP), prolonged the depressor effect of OS-NO but not of Cys-NO, The depressor effect of OS-NO disappeared in AT-125-treated rats within 10 min after administration, which is still shorter than its half-l ife in vitro. Although S-conjugates of L-cysteine, but not of D-cysteine, r apidly enter into cells via an active transport system and disappear from t he circulation, both forms of Cys-NO exhibited similar activity to decrease blood pressure to that of NO. Thus, NO might be rapidly released from Cys- NO in the circulation and shortly exhibited its depressor action. These obs ervations suggested that the circulating OS-NO is rapidly decomposed by gam ma-GTP to form Cys-NO and that the release of NO from both OS-NO and Cys-NO is enhanced significantly in the circulation. (C) 1999 Academic Press.