DYNAMIC ASPECTS OF THE INTERACTION OF S-NITROSOTHIOLS AND REDUCING AGENTS IN THE CIRCULATION

• Published in: Japanese Journal of Pharmacology 1997, Vol.75 (suppl), p.110-110
• Main Authors: Kuang Chang Chien, Emiko Kasahara, Misato Kashiba, Masayasu Inoue
• Format: Article
• Language: Japanese
• ISSN: 0021-5198

Although nitric oxide (NO) generates 5-nitroso-thiols (RS-NO) which exhibit various activities attributable to those of NO, dynamic aspects of their metabolism remain to be elucidated. RS-NO, such as 5-nitroso-glutathione (GS-NO), 5-nitrosocysteine (Cys-NO) and 5-nitroso-albumin (AlbS-NO), exhibit the activity to induce vascular relaxation (EDRE-like activity). To know the in vivo metabolism of RS-NO and their functions, we analyzed the chemical stability of these compounds in fresh plasma (AlbS-NO > GS-NO >> L-Cys-NO D-Cys-NO). The depressor effect of these RS-NO was Cys-NO > GS-NO > AlbS-NO. Although L-form but not D-form amino acids are actively taken up by various cells and tissues, L-Cys-NO and D-Cys-NO exhibited similar activity to decrease blood pressure. This observation suggested that NO might be released from RS-NO in the circulation and the released NO exhibited the depressor effect. In vitro experiments revealed that the reducing agents, such as ascorbic acid and L-cysteine, enhanced the decomposition of RS-NO. Thus, effects of these reducing agents on the depressor action of RS-NO was studied. Kinetic analysis revealed that modulation of ascorbic acid and thiol metabolism specific agents affected the depressor action of RS-NO. These results suggest that NO would be released from the circulating RS-NO in plasma and that both ascorbic acid and L-cysteine modulate the rate of NO liberation thereby regulating the circulatory status. Dynamic aspects of the interaction between NO, RS-NO and the reducing compounds will be discussed.