Specific motivational systems have evolved in many species to favor the eager ingestion of salt during periods of lack and the casual ingestion of excess salt during later periods of plenty. These motivational systems are intimately enmeshed with the cerebral controls of blood pressure and fluid excretion. Salt ingestion exacerbates morbidity during pathological hypertension, cirrhosis, and congestive heart failure, and, ironically, these are times when the motivational systems to ingest salt are activated. This project explores the basic mechanisms that stimulate and inhibit specific salt and water ingestion in health and disease. A particular focus of the study is the renin-angiotensin-aldosterone hormonal system (RAAS) in rats. The RAAS is activated when body sodium stores are low, and angiotensin and aldosterone both act as signals to the brain that water and sodium should be conserved, that blood pressure should be enhanced, and that water and sodium should be found and ingested. One major goal is to determine how the peripheral RAAS activates the central RAAS via forebrain circumventricular organs. A second major goal is to investigate the interactions of the controls of salt appetite and osmotic pressure. A third major goal is to apply these concepts gleaned from studies of normal animals to the analysis of water and sodium intake in animals with bilary cirrhosis. The methods will employ specific brain lesions or brain micro infusions of an antisense oligodeoxynucleotide directed to the mRNA generated the angiotensin II type I receptors, c-fos immunohistochemistry to quantify the relative activation of various brain sites, and direct measurements of blood pressure and drinking behaviors in conscious, freely behaving animals.
