The overall objective of this proposal is to define some of the mechanisms of regulation of cerebral blood flow (CBF) and metabolism (CMR02). One major aim of this proposal will be to integrate the activities of the various disciplines in such a way that the interrelationships will result in a greater contribution than could be achieved if each project were pursued individually. A number of factors are generally considered to exert significant control over the cerebral vasculature. Among these are: central and peripheral nervous system, chemical and metabolic, pharmacologic and mechanical. The precise mechanism(s) by which these factors exert their control at the vascular level is unclear in some cases and unknown in others. The projects outlined in this proposal attempt to clarify some of these mechanisms. In Project I, the specific role of a potential oxygenases sensitive chemoreceptor and its mechanism of chemoreception, i.e. oxygenases, during different types of hypoxemia will be studied. This project will examine the hypothesis that a central chemoreceptor within the brain operates as a major control center of the cerebral vasculature during hypoxia. In Project II, the developmental influences on the cerebrovascular response to hypoxia, and alterations in cerebral perfusion pressure (autoregulation) will be studied. The effects of intraventricular blood on the cerebrovascular bed will also be examined. Project III will systematically evaluate the effects of elevation of intracranial pressure to different levels, at different rates, by different means, in animals of different age on cerebral and peripheral organ blood flow. The control of CBF and CMRO2 during cardiopulmonary resuscitation (CPR) and in particular the methods available to maximize CBF during CPR in young versus adult animals will be studied in Project IV. Finally, the control of pituitary blood flow will be examined in Project V. The hypothesis is that the pituitary vasculature, being specialized in its function, has developed specialized mechanisms for regulating its blood flow which differ from those found in other brain regions. The multidisciplinary approach of the investigators and their different expertise will permit novel and innovative approaches to questions concerning the control of CBF in health and certain disease states.