Abstract
Nitric oxide (.NO) regulates mitochondrial oxygen uptake through reversible high-affinity binding to heme and Cu2+ centers of cytochrome oxidase, and sets adaptive responses to changes in blood flow, O2 availability and hypoxia, thyroid disorders, endotoxemia and cold adaptation. Moreover, subcellular traffic of.NO synthases (NOS) participates in the adjustment of mechanical cardiac efficiency. In isolated beating rat hearts,.NO and bradykinin promote a dosedependent decrease of myocardial O2 uptake and coronary perfusion pressure, without significant variations of the developed left ventricular pressure. Also, in human hearts.NO from NOS isoforms tunes mechanical performance. On these bases, NOS traffic to mitochondria acquires physiological significance. In liver and heart, mitochondrial NOS (mtNOS) was identified as the neuronal isoform (nNOSα) with postranslational modifications. This new class of NOS spatial confinement leads cells to save energy under particular circumstances. Likewise, thyroid status reciprocally regulates mtNOS expression and.NO yield, while it linearly regulates mitochondrial respiration and systemic oxygen uptake. In rats exposed to cold, a clear contribution of.NO from mtNOS to modulation of.VO2 and redistribution of energy expenditure was reported. We conclude that.NOS traffic and mtNOS activity are natural mechanisms to link mitochondria and cardiovascular responses to environmental and endogenously mediated challenges
Keywords: Modulation of oxygen uptake, oxygen delivery, hypoxia, mechanoenergetic coupling, thyroid status, and cold acclimation
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