Cerebral 02 delivery is controlled by both cerebral blood flow and the number of perfused capillaries. Control of the number of perfused cerebral capillaries, in contrast to cerebral blood flow, has not been extensively studied under 02 supply-limited conditions. From our previous work, we know that only about half of the available cerebral capillaries are perfused at rest and this reserve can be utilized during 02 supply stress. Both central and peripheral adrenergic neurons can alter cerebral 02 delivery. Their influence on cerebral 02 delivery appears more important under conditions of 02 lack. We intend to study the effects of various means of reducing 02 supply (anemia, hypoxia, carbon monoxide, hypocapnia) on the perfusion of cerebral capillaries and sympathetic influence on the control of 02 delivery in conscious rats. The primary hypothesis of this grant is: Central and peripheral noradrenergic neurons decrease cerebral 02 delivery by reducing alterations in diffusion distance and cerebral blood flow during 02 supply stress. We also intent to study the relative importance of the cerebral capillary response to 02 lack. To perform these studies, we have developed a method to determine perfused and total capillary density on a regional basis in conscious rat brain. A fluorescent dye is injected to reveal the perfused vessels. The tissue is then stained to reveal the total network. This method, when coupled with measurements of cerebral blood flow with iodoantipyrine and cerebral 02 extraction with microspectrophotometry, will give a complete picture of the cerebral response to 02 supply changes. The importance of peripheral sympathetic innervation, central noradrenergic neurons and the arterial chemoreceptors in the control of cerebral capillary perfusion under conditions of reduced 02 supply will be assessed. This will be determined in experiments involving ablation of the cervical sympathetic ganglia and arterial chemoreceptors. We will study the effects of blockade of central and peripheral adrenoceptors. The importance of changes in intercapillary distance on tissue oxygenation will also be assessed through increases and decreases in cerebral capillary density. Cerebral 02 supply can be controlled at both the arteriolar and capillary level. Through study of the sympathetic nervous system's influence on these two levels of control, we hope to gain a better understanding of its normal control of cerebral 02 supply.
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