N-TERMINAL ATRIAL-NATRIURETIC-PEPTIDE AND ATRIAL-NATRIURETIC-PEPTIDE IN HUMAN PLASMA - INVESTIGATION OF PLASMA-LEVELS AND MOLECULAR CIRCULATING FORM(S) USING RADIOIMMUNOASSAYS FOR PROATRIAL NATRIURETIC PEPTIDE-(31-67), PROATRIAL NATRIURETIC PEPTIDE-(1-30) AND ATRIAL-NATRIURETIC-PEPTIDE-(99-126)

1. The aim of this study was to determine plasma levels of N-terminal atrial natriuretic peptide and atrial natriuretic peptide in normal su bjects and in patients with essential hypertension, cardiac transplant and chronic renal failure, using radioimmunoassays directed towards t he-mid-portion pro-atrial natriuretic peptide (31-67) and pro-atrial n atriuretic peptide (1-30) of the N-terminal atrial natriuretic peptide and atrial natriuretic peptide (99-126). The circulating form(s) of t he immunoreactive N-terminal atrial natriuretic peptide in plasma extr acts has been investigated using all three radioimmunoassays by means of gel filtration chromatography to further clarify the major immunore active molecular circulating form(s) of N-terminal atrial natriuretic peptide in man. 2. The plasma level (mean +/- SEM) of N-terminal pro-a trial natriuretic peptide (31-67) in the normal subjects was 547.2 +/- 32.7 pg/ml (n = 36) and was significantly elevated in patients with e ssential hypertension (730.2 +/- 72.3 pg/ml, P < 0.025, n = 39), in ca rdiac transplant recipients (3214.0 +/- 432.2 pg/ml, P < 0.001, n = 9) and in patients with chronic renal failure (3571.8 +/- 474.1 pg/ml, P < 0.001, n = 11). Plasma levels of N-terminal pro-atrial natriuretic peptide (1-30) and atrial natriuretic peptide were similarly elevated in the same patient groups when compared with the mean plasma values i n the normal subjects. 3. There were positive associations between pro -atrial natriuretic peptide (31-67) and atrial natriuretic peptide, pr o-atrial natriuretic peptide (31-67) and proatrial natriuretic peptide (1-30) and between proatrial natriuretic peptide (1-30) and atrial na triuretic peptide in the normal subjects, hypertensive patients, cardi ac transplant recipients and patients with chronic renal failure. The correlation coefficient for all groups taken together was 0.86 (P < 0. 001, n = 95) for pro-atrial natriuretic peptide (31-67) and atrial nat riuretic peptide, 0.93 (P < 0.001, n = 95) for pro-atrial natriuretic peptide (31-67) and pro-atrial natriuretic peptide (1-30), and 0.82 (P < 0.001, n = 95) for proatrial natriuretic peptide (1-30) and atrial natriuretic peptide. 4. Gel filtration of extracted plasma from cardia c transplant patients and patients with chronic renal failure indicate d a single peak of immunoreactivity for N-terminal atrial natriuretic peptide using both the pro-atrial natriuretic peptide (31-67) and proa trial natriuretic peptide (1-30) radioimmunoassays, suggesting a major single high-molecular-mass circulating immunoreactive N-terminal atri al natriuretic peptide, probably pro-atrial natriuretic peptide (1-98) . Atrial natriuretic peptide immunoreactivity, as measured by the radi oimmunoassay for atrial natriuretic peptide (99-126), showed a separat e and distinct peak from that of the N-terminal atrial natriuretic pep tide, which co-eluted with the synthetic human standard atrial natriur etic peptide (99-126). 5. These results show that immunoreactive N-ter minal atrial natriuretic peptide and atrial natriuretic peptide are el evated in patients with essential hypertension, in cardiac transplant recipients and in patients with chronic renal failure. The major immun oreactive form of N-terminal atrial natriuretic peptide cross-reacting in both the pro-atrial natriuretic peptide (31-67) and pro-atrial nat riuretic peptide (1-30) radioimmunoassays is of a high molecular mass, probably pro-atrial natriuretic peptide (1-98). Since pro-atrial natr iuretic peptide (1-98) is unlikely to cross-react identically with ant ibodies for proatrial natriuretic peptide (31-67) or pro-atrial natriu retic peptide (1-30), this could account for the differences in plasma levels obtained by the assays for pro-atrial natriuretic peptide (31- 67) and proatrial natriuretic peptide (1-30).