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 reticulocyte-rich red blood cell suspensions were aerobically incubated in the absence (control) or in the presence of different concentrations of ISDN. ISDN 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 glucose consumption and lactate accumulation (p<0.05). Levels of all glycolytic intermediates in the presence of ISDN indicate only stimulation of pyruvate kinase activity. ISDN did not alter the concentration of ATP, while increased ADP and AMP levels (p>0.05). In rat reticulocytes under steady-state conditions, 95.4% of overall energy was produced by oxidative phosphorylation but only 4.6% by glycolysis. Due to a reduced coupled oxygen consumption in the presence of ISDN, ATP production via oxidative phosphorylation was significantly diminished. A simultaneous increase of glycolytic ATP production is not enough to ensure constant ATP production. The calculated mean ATP turnover time was prolonged by 199% in the presence of 1.5 mmol/l ISDN. In conclusion, ISDN a) inhibited total and coupled respiration but enhanced uncoupled respiration, b) stimulated glycolysis, c) decreased ATP production and d) prolonged ATP turnover time in rat reticulocytes. These effects were mediated by NO as the effector molecule.

• MeSH
• adenosindifosfát metabolismus   MeSH
• adenosinmonofosfát metabolismus   MeSH
• adenosintrifosfát metabolismus   MeSH
• donory oxidu dusnatého farmakologie   MeSH
• energetický metabolismus účinky léků   MeSH
• glykolýza účinky léků   fyziologie   MeSH
• isosorbiddinitrát farmakologie   MeSH
• krysa rodu Rattus MeSH
• oxid dusnatý metabolismus   MeSH
• oxidativní fosforylace účinky léků   MeSH
• potkani Wistar MeSH
• retikulocyty účinky léků   metabolismus   MeSH
• spotřeba kyslíku účinky léků   fyziologie   MeSH
• vazodilatancia farmakologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adenosindifosfát MeSH
• adenosinmonofosfát MeSH
• adenosintrifosfát MeSH
• donory oxidu dusnatého MeSH
• isosorbiddinitrát MeSH
• oxid dusnatý MeSH
• vazodilatancia MeSH