Role of superoxide, NO and oxygen in the regulation of energy metabolism and suppression of senile diseases

Although nitric oxide (NO) rapidly reacts with molecular oxygen under air a tmospheric conditions, thereby losing its biological functions, the lifetim e of this gaseous radical increases under physiologically low intracellular oxygen tensions. To understand the pathophysiological roles of NO and rela ted molecules in aerobic life, we analyzed the effect of oxygen tensions on the NO-dependent processes in resistance arteries, isolated mitochondria, intact cells and enteric bacteria. Kinetic analysis revealed that NO enhanc ed the generation of cGMP and induced vasorelaxation of resistance arteries more potently under physiologically low oxygen tensions than under hyperba ric conditions. NO reversibly inhibited the respiration of isolated mitocho ndria, intact cells and Escherichia coli; the inhibitory effect was more ma rked under hypoxic conditions than under hyperbaric conditions. Kinetic ana lysis revealed that NO has pivotal action to increase arterial supply of mo lecular oxygen for the generation of ATP in peripheral tissues and to suppr ess energy production in mitochondria and cells in an oxygen-dependent mann er. These functions of NO are enhanced by decreasing oxygen tension in situ and suppressed by locally generated superoxide radicals. Thus, cross-talk of NO, superoxide and molecular oxygen constitutes a supersystem by which t he energy metabolism in cells and tissues is beautifully regulated in a sit e-specific manner depending on the relative concentrations of these three r adical species. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.