The proposed research studies the neuroendocrine control of drinking elicited by eating. Such drinking accounts for the majority of spontaneous fluid intake in mammals including humans, thereby being a major contributor to the maintenance of homeostasis for fluid essential for good health. A two-part working hypothesis describing a histaminergic control of food-related drinking is proposed . that incorporates the renal renin-angiotensin system and angiotensin II as an important component. Project 1 addresses part A (paracrine histaminergic) of the hypothesis by measuring whether food-related drinking is inhibited by: (a) surgical or pharmacological blockade of vagal efferent function; (b) pharmacological blockade of histamine synthesis; (c) pharmacological antagonism of gastric histamine receptors; (d) pharmacological blockade of parietal cell secretory function; (e) pharmacological lesion of gastric vagal afferents; and (f) pharmacological blockade of angiotensin II receptors in brain. Project 1 also measures: (g) whether eating produces decrease of gastric mucosal histamine, and (h) the time-course of decrease in gastric mucosal histamine, development of postprandial dehydration, increased plasma renin activity and drinking behavior. Project 2 addresses part B (renal renin-angiotensin) of the hypothesis by examining the degree to which food-related drinking is inhibited by: (a) renal denervation; (b) pharmacological antagonoism of renal histamine receptors; (c) nephrectomy; (d) pharmacological blockade of synthesis of angiotensin II; and (e) pharmacological blockade of angiotensin II receptors in brain. Project 2 also examines (f) whether pharmacological blockade of gastric vagal afferents inhibits drinking elicited by exogenous angiotensin II. Project 3 addresses the relation among histamine, angiotensin II and dehydration in the control of food-related drinking by: (a) determining whether pharmacological blockade of histamine receptors prevents postprandial dehydration and (b) assessing the effects on food-related drinking of combined pharmacological or surgical blockade of histaminergic and angiotensin II mechanisms. In summary, this work evaluates the working hypothesis for peripheral histaminergic, renal renin-angiotensin and central angiotensin II receptor control of food-related drinking in the rat. The results should penetrate the problem of the relation between physiological mechanisms that activate drinking in advance of dehydration and those mechanisms that activate drinking in response to dehydration.
