Fates and Vascular Action ofS-Nitrosoglutathione and Related Compounds in the Circulation

To know the metabolism of low-molecular-weightS-nitrosothiols (RS-NO) in the circulation, we analyzed the stability and depressor effects ofS-nitrosoglutathione (GS-NO) and thel- andd-forms ofS-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 administration of these compounds. Acivicin (AT-125), an inhibitor of γ-glutamyltransferase (γ-GTP), prolonged the depressor effect of GS-NO but not of Cys-NO. The depressor effect of GS-NO disappeared in AT-125-treated rats within 10 min after administration, which is still shorter than its half-lifein vitro.Although S-conjugates ofl-cysteine, but not ofd-cysteine, rapidly enter into cells via an active transport system and disappear from the 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 observations suggested that the circulating GS-NO is rapidly decomposed by γ-GTP to form Cys-NO and that the release of NO from both GS-NO and Cys-NO is enhanced significantly in the circulation.