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 less than 0.001, n = 50). In healthy individuals a 2-1 (isotonic) saline infusion significantly increased both ANP (99-126) (P less than 0.05, n = 8) and N-terminal ProANP (P less than 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 less than 0.05, n = 8) and 225 min (P less than 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).