CONTROL OF ADH SECRETION AND METABOLISM

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It is well established that vasopressin (ADH) is important in the regulation of the volume and composition of the body fluids. It now appears that ADH is also important in the normal and pathophysiological regulation of arterial pressure. The proposed research is concerned with the control of the plasma ADH concentration and deals specifically with factors affecting secretion of ADH into the blood and the clearance of ADH from the blood by the kidneys and liver. With regard to the control of ADH secretion we shall determine: 1) the central actions of ADH and oxytocin on the plasma ADH concentration under basal conditions and in response to hemorrhage; 2) the role of centrally acting norephinephrine, acetylcholine, dopamine, GABA, prostaglandins, bradykinin, angiotensin II, and enkephalin in the normal and pathophysiological control of ADH release. With regard to the second major area of proposed research, the clearance of ADH from the circulation, we shall identify and evaluate factors which affect the renal and splanchnic clearances of ADH. A thorough understanding of the factors that control the plasma ADH concentration should be of value clinically in dealing with hypertension and with diseases that involve derangements of water and electrolyte metabolism, e.g., congestive heart failure.