Atrial natriuretic factor (
ANF) is a recently discovered, volume responsive
hormone with multiple potent
antihypertensive actions. This article reviews data supporting hypothetical associations between
ANF and
essential hypertension, examines reports of plasma
ANF concentrations in
hypertension, discusses the efficacy of
ANF and its analogs in the treatment of
hypertension, and reviews future issues in
ANF research.
ANF has been shown to elicit vasodilatation, suppress plasma
renin activity, inhibit the synthesis and release of
aldosterone, antagonize sympathetically-mediated release of
norepinephrine, and promote diuresis and natriuresis. A metaanalysis of plasma
ANF concentrations reported in normal and hypertensive subjects reveals a 5 +/- 19 pg/mL (pooled, weighted mean and standard deviation) higher
ANF level in age-matched, untreated hypertensives without evidence of end-organ damage. This difference may be inappropriately low given the increase in atrial filling pressures found in
hypertension. Low doses of
ANF elicit greater reductions in blood pressure in hypertensive subjects than in normals. Recently, inhibitors of the
ANF-degrading
enzyme,
neutral endopeptidase, and of the
ANF "clearance" receptor have enhanced the
antihypertensive actions of endogenous or exogenously administered
ANF. Human studies are currently in progress testing the
antihypertensive efficacy of orally administered
neutral endopeptidase inhibitors. The discovery of
ANF has led to the elucidation of a family of
natriuretic peptides from brain, heart, and kidney, and promises to enlarge our understanding of volume regulation in normal and pathophysiological states. The possibility that
essential hypertension is associated with inappropriately low plasma
ANF levels or altered responsiveness to
ANF may offer new insights into the pathogenesis and treatment of
hypertension.