Mitochondrial Oxidative Phosphorylation: Tissue Oxygen Sensor for Regulation of Coronary Flow
The heart is able to match its metabolic need for oxygen with alterations in oxygen delivery via the coronary blood flow (see for example Alella et al., 1955; Ball et al., 1975; Nuutinen et al., 1982). The mechanisms which elicit this autoregulatory response in coronary flow have been the subject of intensive investigation for many years but they remain incompletely understood. In earlier studies we observed that in suspensions of intact cells the cellular energy state (expressed as [ATP]/[ADP][Pi] is dependent on oxygen tension throughout the physiological range (Wilson et al., 1977; 1979a; 1979b). This dependence was manifested by a progressive increase in the reduction of cytochrome c and lowering of the cytosolic [ATP]/[ADP][Pi] as oxygen tension was lowered. The changes in these two parameters allowed the rate of oxygen consumption, and thus the rate of ATP synthesis, to remain almost undiminished to oxygen tensions below 5 Torr. This oxygen dependence was an expression of the reaction of oxygen with cytochrome c oxidase of the mitochondrial respiratory chain and suggested that oxidative phosphorylation may be the primary tissue “oxygen sensor”. In cardiac tissue the mitochondria sustain continually high rates of ATP production and consume most (>95%) of the oxygen utilized by this tissue. Since ATP is required for muscular work and it and its metabolic products (ADP, Pi, AMP, adenosine) are involved in essentially every cellular metabolic pathway as reactants and regulators, changes in the cellular energy level arising from alterations in tissue oxygen tension can readily be transmitted to the rest of cellular metabolism. In this paper we will summarize some of the data which support the concept that mitochondrial oxidative phosphorylation is the major oxygen sensor for regulation of coronary blood flow.
KeywordsOxygen Tension Coronary Flow Adenosine Receptor Coronary Blood Flow Oxygen Sensor
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