This is an application for continued support of a research program that has been supported by program project grants since 1962. The studies on neural and humoral regulation of endocrine function have now come to focus on the renin-angiotensin systems in the body and the hormones related to them. The present application brings together scientists with expertise in whole animal physiology, cell biology, and molecular genetics to work on six interrelated projects supported by an administrative core, a laboratory service core, and a cell culture core. Project 1 (P.l.: W.F. Ganong) is concerned with the role of the brain in the regulation of circulating angiotensin II, with particular emphasis on hypothalamic control of renin secretion and neuroendocrine control of angiotensinogen secretion. The second project (P.I.: I.A. Reid) is concerned primarily with the interaction between vasopressin and renin secretion, including the possibility that the sympathetic nervous system and atrial natriuretic peptide are involved in the interaction, and with the interesting discovery that stimulation of afferent renal nerves increases vasopressin secretion. The third project (P.I.: C.F. Deschepper) is part of a broader study on tissue renin-angiotensin systems and applies immunocytochemical, molecular, and cell culture techniques to an analysis of the components of the brain renin-angiotensin system and the way angiotensin II is generated in the central nervous system. The fourth project (P.I.: M.K. Steele) is concerned with the mechanism by which the angiotensin II produced in the brain exerts its effects, and employs neuroendocrine models to test the hypothesis that brain angiotensin II acts locally to facilitate the release of norepinephrine, dopamine, and other brain amines. It also explores the function of the brain renin-angiotensin system in the regulation of the secretion of the anterior pituitary gland. The fifth protect (P.I.: T.L. Reudelhuber) explores the regulation of the renin gene and the angiotensinogen gene in the rat and relates this regulation to the factors affecting renin and angiotensinogen secretion. The sixth protect (P.I.: D.G. Gardner) explores the regulation of the atrial natriuretic peptide gene in the brain in relation to brain regulation of fluid and electrolyte metabolism and cardiovascular function. The support requested is for fundamental research, but all the projects are more or less directly related to hypertension, heart failure, diabetes insipidus, and various other cardiovascular and endocrine diseases.
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