N-terminal Atrial Natriuretic Peptide Research Articles

Stability of plasma concentrations of N and C terminal atrial natriuretic peptides at room temperature.

Plasma concentrations of atrial natriuretic peptide (ANP) are increased in patients with ventricular dysfunction and could have a diagnostic role in heart failure. ANP may be unstable after collection, however, limiting any practical diagnostic role. Blood samples were obtained from 18 patients with various conditions. Aliquots were either processed optimally or kept as blood or plasma at room temperature for 6-72 h before processing. Concentrations of C-terminal ANP were lower in specimens kept as blood for 24 and 72 h (mean difference from control -43% and -76%, respectively, (P < 0.001) but N-terminal ANP (extracted) seemed to be stable under all conditions studied (-2% at 24 h and -7% at 72 h, not significant). N-terminal ANP (extracted) is stable and potentially has a role in the diagnosis of heart failure in routine clinical practice.

Atrial natriuretic peptide ANP(1–98) and ANP(99–126) in patients with severe chronic congestive heart failure: Relation to echocardiographic measurements

Studies in patients with moderate heart failure have shown a positive relation between atrial size and plasma atrial natriuretic peptide (ANP)(99–126) concentrations; however, the relation of the hormone level and left atrial size and left ventricular function in patients with severe chronic heart failure has not been determined. Fifty-three patients from the Cooperative North Scandinavian Enalapril Survival Study with severe chronic heart failure were evaluated with M-mode echocardiography and determination of plasma concentrations of ANP(99–126). In 35 patients, the plasma level of N-terminal ANP(1–98) was also measured. A significant negative relation was found between ANP(1–98), ANP(99–126), and left atrial diameter ( r = −.28, P = .05 and r = −.41, P < .005, respectively). Plasma concentrations of both ANP(1–98) and ANP (99–126) were related to left ventricular systolic function as determined by the systolic time interval index ( r = .4, P < .05 and r = .29, P < .05, respectively). A significant improvement of left ventricular systolic function was found in the enalapril group but not in the placebo group. After 6 weeks of therapy, no correlation was found between changes in left atrial size or systolic function or changes in either the ANP(1–98) or ANP(99–126) concentration. The results indicate that high ANP(1–98) or ANP(99–126) plasma concentration is determined by the depressed left ventricular function rather than increased left atrial size in patients with chronic severe heart failure. The findings suggest that the ANP release relation to atrial pressure/atrial size is distorted in severe heart failure.

Plasma Endothelin in Human Essential Hypertension

Plasma endothelin immunoreactivity was measured in normal controls, in mild essential hypertensive patients with no antihypertensive treatment, in moderate to severe hypertensives whose blood pressure was controlled by treatment, and in moderate to severe hypertensives whose blood pressure was not controlled by treatment. Endothelin immunoreactivity levels in plasma in the four groups were similar, but had a positive correlation with blood pressure in hypertensives although not in normotensives. The concentration in plasma of both C-terminal and N-terminal atrial natriuretic peptide also had a positive correlation with blood pressure in these hypertensive patients. We conclude that if plasma immunoreactive endothelin levels represent the result of endothelial production of endothelin, in absence of changes in catabolism of the peptide, essential hypertensive patients do not appear to have increased production of endothelin.

N-Terminal Pro Atrial Natriuretic Peptide in Human Plasma

N-Terminal pro ANP (atrial natriuretic peptide) in human plasma has been measured by radioimmunoassay after extraction on Sep-Pak cartridges. Immunoreactive N-terminal pro ANP circulates in human plasma at higher levels than alpha-hANP (approximately 20-fold higher in normal subjects) and was elevated in patients with essential hypertension, cardiac transplantation and patients with chronic renal failure. In chronic renal failure patients undergoing hemodialysis, C-terminal ANP (ANP 99-126), but not N-terminal ANP, declined significantly after dialysis. Gel filtration experiments demonstrated a single peak of N-terminal ANP immunoreactivity, eluting in parallel with synthetic human pro ANP 1-67, indicating a similar molecular size and the absence of low molecular weight N-terminal fragments.

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).

Immunoreactive N-terminal Pro-Atrial Natriuretic Peptide in Human Plasma: Plasma Levels and Comparisons with α-Human Atrial Natriuretic Peptide in Normal Subjects, Patients with Essential Hypertension, Cardiac Transplant and Chronic Renal Failure

1. Plasma levels of immunoreactive N-terminal pro-atrial natriuretic peptide (N-terminal ANP) have been measured in 25 normal subjects, 29 patients with essential hypertension, six cardiac transplant recipients, seven patients with dialysis-independent chronic renal failure and 11 patients with haemodialysis-dependent chronic renal failure. Plasma was extracted on Sep-Pak cartridges and N-terminal ANP immunoreactivity was measured using an antibody directed against pro-ANP (1-30). 2. Plasma levels of N-terminal ANP (means +/- SEM) were 235.3 +/- 19.2 pg/ml in normal subjects and were significantly raised in patients with essential hypertension (363.6 +/- 36.3 pg/ml), in cardiac transplant recipients (1240.0 +/- 196.2 pg/ml), in patients with chronic renal failure not requiring dialysis (1636.6 +/- 488.4 pg/ml) and patients with chronic renal failure on maintenance haemodialysis (10336.1 +/- 2043.7 pg/ml). 3. There were positive and significant correlations between the plasma levels of N-terminal ANP and alpha-human ANP (alpha-hANP) with individual correlation coefficients of 0.68 within the normal subjects, 0.47 in patients with essential hypertension, 0.78 in patients with dialysis-independent chronic renal failure and 0.68 in patients with haemodialysis-dependent chronic renal failure (P less than 0.05 in every case).(ABSTRACT TRUNCATED AT 250 WORDS)