Add time:08/27/2019         Source:sciencedirect.com

Publisher SummaryThe heart influences renal functions through the release of humoral substances. Dense core granules, resembling secretory granules, were observed in the atria of mammalian hearts. The granules were in close association with the golgi complex and contained a protein material. DeBold and co-workers demonstrated that intravenous injection of atrial, but not ventricular, extracts from rat hearts into anesthetized rats caused a marked but short-lived natriuresis and diuresis and lowered arterial pressure. The unknown material was referred to as atrial natriuretic factor (ANF). The substance was isolated, purified and sequenced; the DNA sequence of the precursor peptide was discovered and receptor sites were identified; the pharmacologic actions of the natriuretic peptide were examined; assays for measurement of ANF were devised, and the clinical effects of ANF were reported. This chapter presents a brief summary of the biology of ANF. The chapter discusses peptide sequence and gene isolation, receptor localization and second messengers, renal pharmacology, and hemodynamic and endocrine effects of ANF. The pharmacology of ANF indicates that it eventually may lead to the discovery of effective agents for the treatment of edema in patients with congestive heart failure, hypertension, renal insufficiency or hepatic cirrhosis. Unlike current diuretic therapy, ANF may prevent compensatory increases in renin release and may be a potassium-sparing diuretic, through direct antagonism of aldosterone release. ANF possesses advantages over many vasodilator agents, in that reflex tachycardia and urinary salt retention are not generally associated with the depressor actions of the atrial peptides. Indeed, initial clinical trials with ANF indicate that the atrial peptides are quite effective in humans.

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