Atrial natriuretic peptide (ANP) is a potent natriuretic and diuretic hormone which may play a role in acute and chronic extracellular volume and arterial pressure homeostasis. Although recent progress has been made defining the effects of ANP on renal function and arterial pressure, there is a limited amount of data quantitating the mechanism of release of ANP under various acute and chronic physiological and pathophysiological conditions. The major objective is to determine the role of atrial pressures (and other possible stimuli) in mediating the release of ANP under various acute and chronic physiological and pathophysiological conditions in conscious, chronically instrumented dogs. In addition, studies will be designed to determine the quantitative importance of ANP's effects on renal function by mimicking plasma levels of ANP comparable to those measured under the various physiologic and pathophysiologic conditions of the present proposal. Specific questions to be addressed are: 1) Are atrial pressures an important stimulus for ANP release in conscious dogs? If so, what is the relationship between right and left atrial pressure and circulating levels of ANP? Are there non-pressure-dependent stimuli for ANP release? 2) Is ANP involved in post-prandial natriuresis, a physiological condition associated with acutely elevated atrial pressures, and extracellular fluid volume? 3) Do chronic increases in sodium intake in normal dogs and in dogs with reduced renal mass (a chronic volume expanded condition) influence circulating levels of ANP and are these conditions associated with changes in right or left atrial pressure? 4) Does ANP play a role in the mechanism of escape from the sodium-retaining effects of aldosterone and angiotensin II? Are atrial pressures elevated during the chronic administration of aldosterone or angiotensin II? Answers to these questions should provide important new information relevant to the understanding of the mechanisms for ANP release during various physiological and pathophysiological conditions.
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