Intraventricular injections of angiotensin II (AII) produce increased blood pressure, vasopressin release, intravascular volume and water intake. Binding studies have localized the organum vasculosum lamina terminalis (OVLT) as a site of AII receptors. In comparisons of normotensive and spontaneously hypertensive rats (SHR), OVLT AII binding levels were 200% higher in the SHR. Extracellular microelectrode recordings from normal rats show neurons in the OVLT to be sensitive to AII. It appears that central AII-sensitive neurons may play a role in blood pressure maintenance and altered sensitivity of these cells to AII may be involved in hypertension. However, little is known of the physiological and morphological differences of these cells in normo- and hypertensive animals or of the mechanisms of AII-sensitivity. The proposed study will attempt to elucidate the physiologicaly mechanisms by which AII affects these neurons and examine whether altered function of these cells is involved in the initiation and maintenance of hypertension. Using normal and hypertensive animals, extracellular recordings will characterize the sensitivity of OVLT neurons to iontophoretically applied AII. Morphometric computerized analysis of these neurons will be conducted and correlated with altered neuronal sensitivity. To examine the specificity of these cells to AII and possible AII-osmotic interactions, in vitro hypothalamic brain slices, containing the OVLT will be used in order to precisely control osmotic pressure. Single-unit activity will be examined for AII sensitivity and separate or simultaneous changes in osmotic pressure. To determine the mechanisms by which AII and osmotic stimuli induce or alter activity, intracellular recordings from OVLT neurons in brain slices will be combined with pharmacological manipulations. In addition, some of the functionally identified neurons will be intracellularly-labeled with horseradish peroxidase to define the morphology and axonal projections of these neurons. These studies will be conducted in animals at various stages of hypertension development and compared to normotensive animals to understand the time course of development and to correlate altered physiological function with structure. The proposed study, thus, will identify the physiological mechanisms of AII-sensitivity and osmosensitivity of neurons in the OVLT and their morphological characteristics. Moreover, differences in neuronal sensitivities will be compared in normal and hypertensive animals in an effort to understand their role in the neural basis of hypertension.