The recently identified atrial natriuretic factors (ANF) are peptides derived from a precursor residing in cardiac atrial granules. They induce natriuresis, relax smooth muscle, inhibit renin and aldosterone secretion, and antagonize the action of angiotensin II. The proposed research will test the hypothesis that the ANF precursor is a prohormone, which when processed to one or more biologically active fragments, participates in the physiological control of extracellular fluid volume and arterial blood pressure. We propose to continue our studies on physiological actions of ANF and to continue working toward development of a radioimmunoassay for ANF. To test the hypothesis that removal of the atrial appendages (major storage sites for ANF) results in decreased ability to excrete salt and water, hemodynamic and fluid volume variables and plasma immunoreactive ANF will be measured in rats that have fully recovered from the surgical stress of atrial appendicectomy and that have been challenged with acute and chronic fluid volume loads. Similar measurements will be made in conscious normotensive and hypertensive rats receiving prolonged (4 days) infusions of synthetic ANF at rates that produce high physiological blood levels of ANF. To test the hypothesis that, at constant renal perfusion pressure, the brain plays a key role in body fluid volume homeostasis, sodium excretion will be measured in decapitated and spinal rats (with cardiovascular and renal function maintained) during acute blood volume expansion. Studies will be conducted to characterize a factor previously found in rat blood and associated with platelets that converts pro ANF to low molecular weight ANF. To test the hypothesis that platelets, in vivo, participate in the activation of exogenously administered pro ANF, pro ANF will be injected into rats with drug-induced thrombocytopenia; the natriuretic and hypotensive responses will be compared with those in control rats. These studies might lead to a better understanding of the pathophysiological mechanisms of disorders involving salt and water homeostasis.
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