Prohormone Atrial Natriuretic Peptides 1-98 and 31-67 Increase with Exercise in Congestive Heart Failure Patients

Recently two peptides consisting of amino acids (a.a.) 1–30 and 31–67 of the N-terminus of the 126 a.a. prohormone of atrial natriuretic factor (pro ANF), as well as atrial natriuretic factor (ANF, a.a. 99–126; C-terminus) were found to have vasodilatory and natriuretic properties. These peptides, as well as ANF, circulate in man as part of the N-terminus of the prohormone. To determine the effect of graded exercise on the circulating concentration of the N-terminus and C-terminus of the ANF prohormone in persons with abnormal salt and water metabolism, 12 individuals with stable congestive heart failure (CHF) were evaluated before and after bicycle exercise testing and the results were subdivided based on the maximal exercise they could achieve. In all of the CHF patients, the circulating concentration of the whole N-terminus (ie, a.a. 1–98), the midportion of the N-terminus (pro ANF 31–67), which circulates as a distinct 3900 molecular weight (m.w.) peptide after being proteolytically cleaved from the N-terminus, and the C-terminus (ANF) increased with exercise. The patients who were able to achieve 100 and 125 watts of workload had a greater maximal oxygen consumption and, in general, a greater percent increase in the circulating concentration of both the N-terminus and the C-terminus of the ANF prohormone than those who had less exercise capacity. Evaluation of the echocardio-graphic, radionucleotide, and the exercise parameters revealed that the circulating concentrations of these atrial peptides correlated best with left atrial dimension, but that left ventricular systolic and diastolic dimensions also correlated positively with their concentrations. Left and right ventricular ejection fractions, as well as the maximal oxygen consumption, correlated negatively with the circulating concentrations of the N-and C-terminal portions of the ANF prohormone.