The long term goal of this program is to understand the relationship between physiological stimuli for arginine vasopressin (AVP) release and the interactions of neurotransmitters which regulate vasopressin secretion. This work will reveal relationships between neurochemical changes and integrative physiology in situations in which AVP contributes to the maintenance of vascular tone such as water restriction and hemorrhage. The focus of the present proposal is to test the hypothesis that gamma- aminobutyric acid (GABA) exerts a tonic inhibition on the release of vasopressin that is modulated by physiological stimuli. Measurements will be made of: 1) neurotransmitter release (GABA and norepinephrine) in the paraventricular nucleus of the hypothalamus (an area controlling AVP secretion) and 2) plasma AVP levels and the subsequent hemodynamic effects of AVP. Using these methods, four specific aims will be addressed. First, it will be determined if GABA exerts a tonic inhibition on AVP release in the resting animal. Secondly, experiments will be performed to determine if GABAergic activity decreases when AVP secretion is stimulated by an osmotic challenge or baroreceptor unloading by lowering arterial pressure. In the third study, the contribution of GABA will be determined to baroreflex-mediated inhibition of AVP release. In these experiments, AVP will be stimulated by an osmotic challenge, then the baroreceptors will be activated by raising arterial pressure. The fourth study will focus on the potential interaction of GABA with the excitatory neurotransmitter, norepinephrine. It is proposed that GABA exerts its inhibitory effect by acting directly to block AVP secretion and indirectly to interfere with norepinephrine release. These studies will provide significant new insights into the neurochemical mechanisms controlling the physiological regulation of AVP release.
