Relative natriuretic activities of synthetic atriopeptins I, II and III.

Recent evidence indicates that mammalian atria contain a series of peptides which possess potent natriuretic activity. Using a sensitive and reproducible bioassay developed by this laboratory, the natriuretic and diuretic activities of three peptides, atriopeptins I, II, and III (21, 23 and 24 amino acids, respectively) were compared. Bioassays were conducted in pentobarbital-anesthetized male Sprague-Dawley rats weighing 300-350 grams. At doses ranging from 0.33 to 3.0 micrograms, no significant differences in natriuretic or diuretic activities were observed between the three peptides. The time courses of the natriuretic and diuretic responses to these peptides were also identical. The finding that atriopeptin I (21 amino acids) possesses natriuretic activity equal to that of atriopeptins II and III suggests that the C-terminus residues of atriopeptin III (Phe-Arg-Tyr) are not necessary for full expression of natriuretic activity. However, since several previous reports have indicated that atriopeptin I is considerably less potent as a natriuretic than we report here, perhaps a cautionary note should be sounded concerning the conditions required to produce or to retain full biologic activities of the synthetic atriopeptins.