Numerous studies show that angiotensin of peripheral origin stimulates receptors in the central nervous system to initiate compensatory reactions to fluid loss. These include increased arterial pressure, vasopressin release, and thirst. Investigations indicate that neuronal structures located in the anterior ventral third ventricle (AV3V) region are necessary for the detection of peripheral anqiotensin. These same structures are also implicated in osmoreception and sensing of brain-borne angiotensin. Recent anatomical studies postulate that angiotensin, and perhaps osmoreceptors, in the subfornical organ (SFO) and the organum vasculosum lamina terminalis (OVLT) send excitatory neural input to the nucleus medianus (NM) to mobolize the above compensatory mechanisms. Interest in these structures has been heightened by studies showing that destruction of this region prevents a number of experimental forms of hypertension, and that altered brain angiotensin levels and neuronal sensitivity in this region are found in the spontaneously hypertensive rat. To date, however, little is known of the neurophysiology of the interconnections between these structures. During the past two years our studies have concentrated on angiotensin II sensitive neurons located in the OVLT region. This proposal is a continuation of that project in which we will expand our studies to investigate the electrophysiology of interconnections within the AV3V region. Utilizing a recently developed AV3V in vitro brain slice we will investigate the affects of SFO and OVLT stimulation on NM neurons. Using this approach we will carefully examine the neuropharmacology of these projections, some of which are angiotensinergic. Using intact preparations, we will also characterize the influence of SFO, OVLT and NM activation on identified supraoptic (SON) and paraventricular (PVN) nucleus magnocellular and parvocellular neurons. In another series of experiments, neuronal activity in the NM will be examined for sensitivity and integration of ascending cardiovascular information following pharmacologic alterations in arterial pressure and direct electrical activation of afferent nerves. The purpose of the proposed study is to begin a careful electrophysiologic and pharmacological investigation of the neuronal structures located in the AV3V region, concentrating on postulated angiotensinergic pathways. The results of these studies should provide important new information about the neural regulation of arterial pressure and fluid balance, as well as, more general information about the function of central peptidergic pathways.
