Oxygen sensors in vascular smooth muscle.

Inhibition or activation of cellular function due to acute decreases in PO2 can be considered in terms of two different processes: 1) a sensor that monitors PO2 decreases and 2) transduction systems directed from the O2 sensor to reactions that control cellular function. We used the norepinephrine-contracted aortic smooth muscle model to study the nature of the O2 sensor and transduction system during decreased PO2-evoked relaxations. The phosphorylation potential, a measurement of kinetic energy required for ATP hydrolysis, was decreased to 30% of control at the onset of relaxation and progressively fell as muscle relaxed. The free inorganic phosphate intracellular concentration ([Pi]) was experimentally increased approximately 0.6 mM during transients that followed a rapid decrease in PO2. Relaxations to 80% of maximal force were more rapid under conditions of an augmented [Pi] than in control rings, and they occurred at a higher phosphocreatine concentration and phosphocreatine-to-free creatine ratio but at the same phosphorylation potential. Results support the operation of a cytochrome aa3 O2 sensor in the mechanism of decreased PO2-evoked relaxations and implicate an increase in [Pi] and a decrease in kinetic energy in the transduction mechanism directed at rate-limiting reactions that control force.