Oxygen delivery to the tissues and mitochondrial respiration.

In mammals, the O2 transport from the inspired air to the tissues is made by convective and diffusive mechanisms. The convective mechanisms are provided by the cardio-respiratory system and comprised by the basic variables of cardiac output and blood O2 content. Microcirculation in arterioles and capillaries is adjusted to match the O2 demand of local tissues. Endothelium-generated NO diffuses to the smooth muscle of microvessels and produces vasodilation that increases circulatory time in the capillaries and allows a more effective O2 extraction in the tissues. Once within the tissue, O2 diffuses to mitochondria where it is reduced in an exergonic process coupled to ATP synthesis. Both, O2 and ATP are the two most homeostatic intracellular species. In heart and muscle, both species show unchanged levels with 25-100 times increases in work load and ATP turnover rate. The linear rates of O2 uptake shown by tissue slices and perfused organs are interpreted as a fast switching of mitochondria between metabolic state 3 (with a fast rate of O2 uptake and ATP synthesis) and state 4 (with a slow rate of O2 uptake and no ADP phosphorylation). Endogenous mitochondrial NO, produced by mtNOS, sustains the concept of a physiological functional activity of this enzyme in regulating mitochondrial and cellular O2 uptake.