Effects of nitric oxide donor, isosorbide dinitrate, on energy metabolism of rat reticulocytes

Since nitric oxide (NO) in many cells is involved in energy metabolism, the aim of this study was to evaluate the role of isosorbide dinitrate (ISDN), a NO donor, in energy metabolism of rat reticulocytes, particularly due to their high content of hemoglobin - an effective scavenger of NO. Rat retic ulocyte-rich red blood cell suspensions were aerobically incubated in the a bsence (control) or in the presence of different concentrations of ISDN. IS DN decreased total and coupled oxygen consumption (p<0.05) while increased uncoupled oxygen consumption (p<0.05) in a dose- and time-dependent manner. This was followed by enhancement of glycolysis, as measured by increased g lucose consumption and lactate accumulation (p<0.05). Levels of all glycoly tic intermediates in the presence of ISDN indicate only stimulation of pyru vate kinase activity. ISDN did not alter the concentration of ATP, while in creased ADP and AMP levels (p<0.05). In rat reticulocytes under steady-stat e conditions, 95.4 % of overall energy was produced by oxidative phosphoryl ation but only 4.6 % by glycolysis. Due to a reduced coupled oxygen consump tion in the presence of ISDN, ATP production via oxidative phosphorylation was significantly diminished. A simultaneous increase of glycolytic ATP pro duction is not enough to ensure constant ATP production. The calculated mea n ATP turnover time was prolonged by 199 % in the presence of 1.5 mmol/l IS DN. In conclusion, ISDN a) inhibited total and coupled respiration but enha nced uncoupled respiration, b) stimulated glycolysis, c) decreased ATP prod uction and d) prolonged ATP turnover time in rat reticulocytes. These effec ts were mediated by NO as the effector molecule.