A potent fast-acting natriuretic substance was recently identified in extracts of human and rat heart atria and tentatively in extracts of human urine.
The specific aims of this research are to purify the atrial natriuretic factor (ANF) to homogeneity, ascertain its chemical, physical, and physiological properties and determine if the excretion of ANF is altered in hypertensive man and rats. The information obtained from this project is a prerequisite to our long-term objectives, which are to determine if ANF plays a physiological role in sodium excretion and, if so, examine its function in hypertensive man and rats. Even if ANF proves to have but little intrinsic physiological importance, an understanding of its chemical structure and the mechanisms by which this endogenous molecule produces natriuresis of such rapid onset and great magnitude might provide valuable insights about renal function and lead to the possible development of new diuretic/natriuretic agents. An outline of the studies proposed are: 1) improve the bioassay of ANF currently used in our laboratory; 2) determine the effect of ANF on glomerular filtration rate and hemodynamics; 3) purify ANF and characterize its chemical and physical properties; 4) improve the protocol currently used for recovering ANF from human and rat urine; 5) establish that the ANF we have tentatively identified and recovered from urine is similar in nature to the ANF in atrial extracts; and 6) determine if the excretion of ANF is modified in man and rats with genetic hypertension consuming varied and low sodium diets. ANF may play a role in the regulation of sodium excretion, and information regarding its possible physiological actions might help explain the well-known, but incompletely understood, relationship between salt intake and hypertension.
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