NEGATIVE FEEDBACK OF ATRIAL NATRIURETIC PEPTIDES

The present investigation was designed to determine whether atrial nat riuretic peptides consisting of amino acids 1-30 [ie. pro-ANF-(1-30)], 31-67 [i.e. pro-ANF(31-67)], 79-98 [ie. pro-ANF-(79-98)], and 99-126 [i.e. atrial natriuretic factor (ANF)] of 126-amino acid ANF prohormon e have a negative feedback on their own and each others' release. Thir ty healthy human subjects were studied with infusion of 100 ng/kg BW m in for 60 min of each of the respective peptides. Pro-ANF-(1-30) decre ased the circulating concentrations of pro-ANF-(31-67) and ANF 51% and 89%, respectively. Pro-ANF-(31-67) decreased the circulating concentr ation of ANF by 55% and the peptides immunologically recognized by the pro-ANF-(1-30) RIA by 58% [this assay recognizes pro-ANF-(1-30) (50%) and pro-ANF-(1-98) (50%)]. Pro-ANF-(79-98) decreased the circulating concentration of ANF by 40%, pro-ANF-(31-67) by 31%, and the peptides recognized by the pro-ANF(1-30) RIA by 46%. ANF decreased the circulat ing concentration of pro-ANF-(31-67) by 40% and the peptides recognize d by pro-ANF-(130) RIA by 38%. Infusion of pro-ANF-(1-30), -(31-67), - (79-98), and (99-126) also decreased the excretion of the other atrial natriuretic peptides measured in the urine by 32-84%. Infusion of veh icle only did not result in any decrease in these atrial natriuretic p eptides in either plasma or urine. These data taken together indicate that each of the respective atrial natriuretic peptides inhibits the r elease, rather than breakdown, of each other, as increased breakdown w ould have resulted in their urinary concentrations being increased. Th is study further indicates that because pro-ANF-(1-98) was decreased i n the circulation secondary to pro-ANF-(31-67) and pro-ANF-(79-98) inf usions, they inhibit their own release, as they are both derived from pro-ANF-(1-98).