Nitric Oxide-Independent effects of nitric oxide donors on energy metabolism in erythrocytes

In order to study the roles of nitric oxide (NO) in various biological even ts, several types of NO-releasing agents have been extensively used. Althou gh both NO and its donors and/or their decomposed products may have biologi cal activities, most of the cellular responses to these donors have been po stulated to reflect NO-dependent events. Among the various NO donors, 1-hyd roxy-2-oxo-3-(N-methyl-aminopropyl) -3-methyl-1-triazene (NOC7), 3-morpholi nosydnonimine N-ethylcarbamide (SIN-1), S-nitrosoglutathione, S-nitrosocyst eine (CysNO), and related nitrosothiols are commonly used agents. To invest igate the biological activities of these donors and their decomposed produc ts, we tested their effects on energy metabolism in erythrocytes. When incu bated with freshly prepared erythrocytes, NOC7,Cys-NO, and their decomposed products, but not NO and its oxidized metabolites, nitrite and nitrate, de creased cellular ATP levels. Although SIN-1 generates both NO and superoxid e radical thereby forming peroxynitrite (ONOO-), this donor had no apprecia ble effect on cellular ATP levels, even in the presence of superoxide dismu tase. These results indicate that NOC7 and CysNO and/or their decomposed pr oduct(s), but not NO and its oxidised metabolites, are responsible for the decrease in cellular ATP levels. Thus, the: effects of not only NO and its oxidized metabolites (NO2- NO3-), but also NO donors and their decomposed p roducts, should be taken into account when attempting to understand the mec hanism of biological responses induced by NO donors. (C) 2000 Elsevier Scie nce Inc.