The objectives of this proposal are to determine: (1) the PO2 range over which the blood vessel wall is sensitive to oxygen; (2) the mechanism whereby oxygen modulates the contractile response of blood vessels; and (3) the respective roles of vascular smooth muscle and endothelium in oxygen sensing. Experiments will be conducted on arterial vessels from the rabbit. Helical strips or vascular rings will be mounted in chambers containing physiologic salt solution. The relation between isometric force and solution PO2 will be obtained for graded reductions in PO2, allowing us to determine critical solution PO2. Oxygen consumption will be measured as a function of PO2 to determine whether the critical PO2 for oxygen consumption is equal to that for force development. PO2 profiles within the vascular wall will be measured to determine whether the critical PO2 for force development corresponds to the onset of hypoxia within the preparation. High energy phosphate levels will be measured to determine whether there is evidence for energy-limited contraction during hypoxia. The relative contribution of respiration and glycolysis to overall energy production will be determined during graded decreases in solution PO2. The role of adenosine as a mediator of oxygen-induced contractile responses will be investigated using adenosine deaminase and by measuring adenosine levels in and production rates by vascular wall preparations. The results of this study should delineate the role of the blood vessel wall in sensing changes in blood oxygen levels (as occur in exercise, hypoxemia, and ischemia) and provide a coherent view of oxygen chemoreception in the peripheral vasculature.
| Pittman, R N; Graham, B A (1986) Sensitivity of rabbit aorta to altered oxygen tension. Adv Exp Med Biol 200:373-83 |
| Pittman, R N (1986) Interaction between oxygen and the blood vessel wall. Can J Cardiol 2:124-31 |
