Inhibitors of ANF metabolism. Potential therapeutic agents in cardiovascular disease.

A trial natriuretic factor (ANF), a 28-amino acid peptide hormone synthesized and secreted from atrial myocytes, has been suggested to play an important role in the regulation of extracellular fluid volume and arterial pressure. Physiological and pharmacological doses of this peptide have been shown to produce natriuresis and diuresis, vasorelaxation, and inhibition or antagonism or both of important hormonal regulatory systems, such as the reninangiotensin-aldosterone system.1"2 Because of its multiple actions, ANF is thought by many investigators to play an important role in balancing or modulating the various sodium-retaining systems of the body. Obviously, the diverse actions of ANF have also led many investigators to speculate that ANF may be a potentially important therapeutic tool for the treatment of sodium-retaining diseases such as congestive heart failure and hypertension. The peptide structure of ANF, however, limits its therapeutic usefulness since peptides of this length can only be administered intravenously. This limitation has been overcome by the recent development of compounds which alter the metabolism of endogenously produced ANF. Inhibition of important degradative