We propose to extend our investigations of the mechanisms which regulate blood flow into and within the median eminence. As it is the rostral region of the neurohypophysis - a brain diverticulum - its blood flow could be regulated by local functional and metabolic needs as in the brain. We will measure regional blood flow and amino acid influx using 14C-iodoantipyrine (IAP) and 14C-phenylalanine in the hypothalamic neurosecretory nuclei of awake rats under defined conditions. We will correlate these measurements with plasma levels of pituitary hormones measured by radioimmuno-assay and bioassay and median eminence blood flow measured by 14C-isopropyl-iodoamphetamine (IMP). As the median eminence lacks a blood brain barrier and has a central catecholaminergic innervation, its blood flow may be regulated by circulating or by locally released catecholamines. We will measure ovine median eminence blood flow by the radiolabeled microsphere technique prior to and following the infusion of catecholamine agonists and antagonists. We will also employ transmission electron microscopy, immunohistochemistry, and 6-OH-DA lesioning of the rat brain stem to demonstrate neurohemal contact with median eminence capillaries by terminals of the noradrenergic reticulo-infundibular tract as well as by dopaminergic terminals of the tubero-infundibular tract; and hence, a means by which locally released norepinephrine as well as dopamine can reach precapillary arterioles on the surface of the median eminence. As the median eminence is characterized by a regional segregation of neurosecretory systems, mechanisms which control regional blood flow within the median eminence assume an important role in neural control of pituitary function. We will employ computer graphics techniques in conjunction with transmission electron microscopy to reconstruct the microvascular units in the median eminence and to ascertain if sphincters at the origin of these units can control blood flow into discrete regions of the median eminence. The pituitary gland is essential for a successful response to illness or trauma. Much is known of the neural mechanisms which deliver hypothalamic hormones to median eminence capillaries. Little is known of the vascular mechanisms which regulate transport of these hormones to their target cells in the pars distalis to regulate their function under normal and pathologic conditions. This proposal will illuminate these vascular mechanisms which permit the brain to control pituitary function.
