Heparin Interferes with the Biological Effectiveness of Atriopeptin

The chromatographic mobility of atriopeptin-28 or of the prohormone is markedly altered by preincubation of the pep tides with heparin before separation on reverse-phase high performance liquid chromatography. Protamine prevented the heparin effect and reestablished the original migration pattern of the atrial peptides. The addition of heparin to either rat or human plasma samples did not interfere with the atriopeptin immunoreactivity. The influence of heparin on the biological activity of the atriopeptin-28 in anesthetized rats was also investigated. Infusion of heparin (30 U/min) significantly reduced the dose-dependent fall of blood pressure produced by atriopeptin-28, but did not interfere with the hypotensive effect of nitroglycerin. Similarly, infusion of heparin in volume-expanded rats markedly decreased the diuresis produced by atriopeptin-28 without altering the urine volume excreted in response to furosemide. These data suggest that the highly charged molecule heparin can modify the physical and biological properties of atriopeptins, perhaps by binding to the numerous arginine residues (i.e., 5 arginine residues in atriopeptin-28) in the atriopeptin molecules.