Gamma aminobutyric acid (GABA) is a major inhibitory neurotransmitter in the brain. Central administration of GABA and its agonists lowers blood pressure, but it is little known as to which and how GABA systems are involved in the cardiovascular regulation. The primary goal of this proposal is to elucidate the role of GABAergic neurons in regulation of the vasopressin (VP) neurons in (a) the paraventricular hypothalamic nucleus (PVN) - nucleus tractus solitarius (NTS) autonomic pathway, and (b) the PVN - pituitary neuroendocrine axis. However, my long-term objective is to study mechanisms by which central GABAergic neurons modulate blood pressure. Electron microscopic immunocytochemistry, high performance liquid chromatography, radiometric assay (for glutamate decarboxylase, GAD), radioimmunoassay (for detecting VP contents), in situ hybridization (for studying VP mRNA), and quantitative receptor autoradiography will be applied to evaluate the GABA and VP neurons of spontaneously hypertensive (SHR) rats. More specifically, this proposal is: 1) to reveal GABAergic neurons supplying the PVN, lateral """"""""circumventricular"""""""" region (LCV), and NTS; 2) to characterize GAD activities, GABA synaptogenesis, GABA contents, GABA turnover and GABA receptors in the PVN, LCV, and NTS of SHR rats; 3) to evaluate the relationship between GABA parameters and VP parameters (i.e., VP mRNA and VP contents) in the PVN; 4) to study whether receptors for benzodiazepines (which are closely interacted with endogenous GABA), are in conjunction with GABA receptors to associate with hypertension; 5) to determine whether and how changes of GABA/VP parameters in the PVN are correlated with GABA/VP parameters in the NTS during the development of hypertension; and 6) to verify that there are functional GABA receptors in the PVN to regulate VP, by studying VP contents in the NTS, pituitary and plasma after microinjections of a GABA antagonist into the PVN. These studies may provide new information on the neural basis of hypertension associated with GABA/VP neurons, which will be useful for drug developments aimed at the treatment or prevention of hypertension.
