The long-term objectives of this research program are to define those humoral mechanisms involved in hypertension and heart failure. The present proposal is focused on a recently discovered family of cardiac atrial peptides collectively referred to as atrial natriuretic factor (ANF). These ANF peptides have potent natriuretic, diuretic and smooth muscle relaxant activities. Alterations in the synthesis, release and/or target-tissue recognition of ANF may be important in the pathogenesis of hypertension and heart failure and, also, in fluid and electrolyte homeostasis. Using a sensitive radioimmunoassay for ANF, it is planned to study those factors which alter the secretion of endogenous ANF in the conscious dog. These experiments will relate the circulating plasma levels of immunoreactive ANF to changes in sodium intake and balance, systemic hemodynamics, renal hemodynamic and excretory functions, and the activity of the renin-angiotensin-aldosterone system. Sequential determinations of plasma ANF levels will be made in conscious dogs with experimental renal hypertension, or with experimental heart failure and ascites. Also, the hemodynamic and renal responses to acute infusions of synthetic ANF will be examined in these conscious dogs with hypertension or heart failure. Additional studies are planned to evaluate the effect of chronic administration of salt-retaining steroids and of vasopressin on plasma concentrations of immunoreactive ANF in conscious dogs. Finally, the relationship between endogenous plasma ANF and dopaminergic control of aldosterone will be examined.
