Concentrations of N-terminal ProANP in human plasma: Evidence for ProANP (1–98) as the circulating form

Plasma levels of immunoreactive N-terminal ProANP have been measured in plasma from 19 healthy individuals, 15 patients with essential hypertension, 8 cardiac transplant recipients and 8 patients with chronic renal failure using two separate radioimmunoassays (RIAs), one directed against ProANP (1–30) and the other against ProANP (79–98). The mean concentrations of ProANP (1–30) and ProANP (79–98) were elevated in these groups of patients. There were positive correlations between levels of ProANP (1–30) and ProANP (79–98), with a correlation coefficient of 0.97 ( P < 0.001, n = 50). In healthy individuals a 2-1 (isotonic) saline infusion significantly increased both ANP (99–126) ( P < 0.05, n = 8) and N-terminal ProANP ( P < 0.005, n = 8) within 15 min of the end of the infusion. Plasma N-terminal ProANP levels were still significantly elevated after 75 min ( P < 0.05, n = 8) and 225 min ( P < 0.05, n = 8), by contrast ANP (99–126) had returned to basal values. Gel filtration of plasma extracted on Sep-Pak C-18 from normal individuals and patients gave a single immunoreactive peak for N-terminal ProANP as measured by both N-terminal ProANP assays, indicating an absence of small N-terminal fragments and the presence of a single high molecular weight form. These studies demonstrate that the major circulating N-terminal ANP in man is probably ProANP (1–98) and that it is cosecreted with ANP (99–126).