The Circadian Rhythm of the N-Terminus and C-Terminus of the Atrial Natriuretic Factor Prohormone

Circadian variation in the circulating concentrations of the N-terminal and C-terminal portions of the atrial natriuretic factor prohormone (pro ANF) was evaluated in 8 men, ages 41–47, who have been followed for 19 years with respect to circadian variation in physiological variables including blood pressure and clinical chemistries. The N-terminus of the ANF prohormone contains two peptides consisting of amino acids 1–30 and 31–67 while the C-terminus contains 1 peptide (amino acids 99–126) of this 126 amino acid prohormone which lower blood pressure and have natriuretic properties. To determine if either the N-terminus and/or the C-terminus of the prohormone have a circadian variation in their circulating plasma concentrations these 8 men had blood samples obtained for radiommunoassay every 3 hr during a 24-hr period. Three radiommunoassays which immunologically recognize (1) the whole N-terminus (i.e. amino acids 1–98), (2) the midportion of the N-terminus (amino acids 31–67) and (3) the C-terminus (amino acids 99–126) of the ANF prohormone were utilized. The whole N-terminus, the midportion of the N-terminus which circulates after being proteolytically cleaved from the rest of the N-terminus, and the C-terminus each had a peak circulating concentration between 0400 and 0700 which were significantly (P < 0.001) higher than their concentrations at any other time throughout the 24-hr period. It was concluded that there is a circadian rhythm in both the N-terminus and C-terminus of the ANF prohormone with peak plasma concentrations near the 24-hr nadir in blood pressure suggesting a possible cause for this blood pressure nadir since both the N-terminus and C-terminus of this prohormone contain blood pressure lowering peptides.