Plasma Concentrations and Comparisons of Brain Natriuretic Peptide and Atrial Natriuretic Peptide in Normal Subjects, Cardiac Transplant Recipients and Patients with Chronic Renal Failure

1992 ◽  
Vol 82 (s26) ◽  
pp. 29P-29P
Author(s):  
M G Buckley ◽  
D Sethi ◽  
S H Jennison ◽  
J B Eastwood ◽  
N D Markandu ◽  
...  
1989 ◽  
Vol 77 (5) ◽  
pp. 573-579 ◽  
Author(s):  
M. G. Buckley ◽  
G. A. Sagnella ◽  
N. D. Markandu ◽  
D. R. J. Singer ◽  
G. A. MacGregor

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 TV-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 (10 336.1 ± 2043.7 pg/ml). 3. There were positive and significant correlations between the plasma levels of TV-terminal ANP and α-human ANP (α-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 < 0.05 in every case). 4. Gel filtration behaviour on Sephadex G-50 of the immunoreactive N-terminal ANP from Sep-Pak extracts of plasma from normal subjects or patients was consistent with a single peak having an elution volume corresponding to that of human pro-ANP (1–67) standard. 5. These studies demonstrate that the N-terminal pro-ANP peptide is co-secreted with α-hANP in both normal subjects and patients with cardiovascular/renal disease. The higher levels of the N-terminal ANP may reflect differences in the rate of elimination from the circulation but the exact structure and functional significance of the circulating N-terminal ANP remains to be established.


1994 ◽  
Vol 87 (3) ◽  
pp. 311-317 ◽  
Author(s):  
M. G. Buckley ◽  
N. D. Markandu ◽  
G. A. Sagnella ◽  
G. A. MacGregor

1. The aim of this study was to determine plasma levels of N-terminal atrial natriuretic peptide and atrial natriuretic peptide in normal subjects and in patients with essential hypertension, cardiac transplant and chronic renal failure, using radioimmunoassays directed towards the mid-portion pro-atrial natriuretic peptide (31-67) and pro-atrial natriuretic peptide (1-30) of the N-terminal atrial natriuretic peptide and atrial natriuretic peptide (99-126). The circulating form(s) of the immunoreactive N-terminal atrial natriuretic peptide in plasma extracts has been investigated using all three radioimmunoassays by means of gel filtration chromatography to further clarify the major immunoreactive molecular circulating form(s) of N-terminal atrial natriuretic peptide in man. 2. The plasma level (mean ± SEM) of N-terminal pro-atrial natriuretic peptide (31-67) in the normal subjects was 547.2 ± 32.7 pg/ml (n = 36) and was significantly elevated in patients with essential hypertension (730.2 ± 72.3 pg/ml, P < 0.025, n = 39), in cardiac 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 in the normal subjects. 3. There were positive associations between pro-atrial natriuretic peptide (31-67) and atrial natriuretic peptide, pro-atrial natriuretic peptide (31-67) and pro-atrial natriuretic peptide (1-30) and between pro-atrial natriuretic peptide (1-30) and atrial natriuretic peptide in the normal subjects, hypertensive patients, cardiac 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 natriuretic 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 pro-atrial natriuretic peptide (1-30) and atrial natriuretic peptide. 4. Gel filtration of extracted plasma from cardiac transplant patients and patients with chronic renal failure indicated a single peak of immunoreactivity for N-terminal atrial natriuretic peptide using both the pro-atrial natriuretic peptide (31-67) and pro-atrial natriuretic peptide (1-30) radioimmunoassays, suggesting a major single high-molecular-mass circulating immunoreactive N-terminal atrial natriuretic peptide, probably pro-atrial natriuretic peptide (1-98). Atrial natriuretic peptide immunoreactivity, as measured by the radioimmunoassay for atrial natriuretic peptide (99-126), showed a separate and distinct peak from that of the N-terminal atrial natriuretic peptide, which co-eluted with the synthetic human standard atrial natriuretic peptide (99-126). 5. These results show that immunoreactive N-terminal atrial natriuretic peptide and atrial natriuretic peptide are elevated in patients with essential hypertension, in cardiac transplant recipients and in patients with chronic renal failure. The major immunoreactive form of N-terminal atrial natriuretic peptide cross-reacting in both the pro-atrial natriuretic peptide (31-67) and pro-atrial natriuretic peptide (1-30) radioimmunoassays is of a high molecular mass, probably pro-atrial natriuretic peptide (1-98). Since pro-atrial natriuretic peptide (1-98) is unlikely to cross-react identically with antibodies for pro-atrial natriuretic peptide (31-67) or pro-atrial natriuretic peptide (1-30), this could account for the differences in plasma levels obtained by the assays for pro-atrial natriuretic peptide (31-67) and pro-atrial natriuretic peptide (1-30).


1994 ◽  
Vol 87 (3) ◽  
pp. 319-322 ◽  
Author(s):  
Kazuhito Totsune ◽  
Kazuhiro Takahashi ◽  
Osamu Murakami ◽  
Fumitoshi Satoh ◽  
Masahiko Sone ◽  
...  

1. C-type natriuretic peptide is a neuropeptide, which is also produced by the vascular endothelial cells. Plasma immunoreactive C-type natriuretic peptide concentrations in patients with various diseases have not yet been studied. 2. Plasma immunoreactive C-type natriuretic peptide concentrations were studied by radioimmunoassay in normal subjects, patients with congestive heart failure, non-dialysed patients with chronic renal failure and haemodialysis patients with chronic renal failure. The C-type natriuretic peptide levels were compared with the levels of atrial natriuretic peptide and brain natriuretic peptide. 3. Plasma immunoreactive C-type natriuretic peptide concentrations were greatly elevated in patients with chronic renal failure [non-dialysed, 13.0 ± 4.2 pmol/l (mean ± SEM), n = 9, P < 0.01) compared with normal subjects (4.4 ± 0.4 pmol/l, n = 26); haemodialysis, 16.1 ± 2.1 pmol/l, n = 13, P < 0.01], but not in patients with congestive heart failure (New York Heart Association Class II-IV, 3.0 ± 0.7 pmol/l, n = 11, P > 0.05). Plasma immunoreactive atrial natriuretic peptide and brain natriuretic peptide concentrations were elevated both in patients with congestive heart failure and in haemodialysis patients with chronic renal failure. 4. Reverse-phase high performance liquid chromatography showed that immunoreactive C-type natriuretic peptide in plasma from normal subjects and haemodialysis patients was eluted in the positions of C-type natriuretic peptide −22 and −53. 5. These findings suggest that C-type natriuretic peptide is a non-cardiac circulating hormone and participates in the cardiovascular regulation in a different manner from atrial natriuretic peptide and brain natriuretic peptide.


1992 ◽  
Vol 83 (4) ◽  
pp. 437-444 ◽  
Author(s):  
M. G. Buckley ◽  
D. Sethi ◽  
N. D. Markandu ◽  
G. A. Sagnella ◽  
D. R. J. Singer ◽  
...  

1. We have developed a radioimmunoassay for the measurement of immunoreactive brain natriuretic peptide (1–32) in human plasma. Simultaneous measurements of atrial natriuretic peptide have also been carried out to allow for direct comparison between circulating brain natriuretic peptide and atrial natriuretic peptide. Plasma levels of immunoreactive brain natriuretic peptide (means ± sem) were 1.1 ± 0.1 pmol/l in 36 normal healthy subjects and were significantly elevated in cardiac transplant recipients (18.8 ± 3.9 pmol/l, n = 12) and in patients with dialysis-independent (8.8 ± 1.5 pmol/l, n = 11) or dialysis-dependent (41.6 ± 8.8 pmol/l, n = 14) chronic renal failure. Similarly, in these groups of patients plasma levels of atrial natriuretic peptide were also significantly raised when compared with those in the group of normal healthy subjects. 2. The plasma level of atrial natriuretic peptide was significantly higher than that of brain natriuretic peptide in normal subjects and in patients with dialysis-independent chronic renal failure, with ratios (atrial natriuretic peptide/brain natriuretic peptide) of 2.8 ± 0.2 and 2.2 ± 0.3, respectively. However, in both cardiac transplant recipients and patients on dialysis plasma levels of atrial natriuretic peptide and brain natriuretic peptide were similar, with ratios of 1.3 ± 0.2 and 1.0 ± 0.1, respectively, in these two groups. 3. Plasma levels of brain natriuretic peptide and atrial natriuretic peptide were significantly correlated in the healthy subjects and within each group of patients. When all groups were taken together, there was an overall correlation of 0.90 (P<0.001, n = 73). 4. Patients on dialysis had the highest plasma levels of both brain natriuretic peptide (41.6 ± 8.8 pmol/l, n = 14) and atrial natriuretic peptide (41.3 ± 9.4 pmol/l, n = 14) and the levels of both peptides declined significantly after maintenance haemodialysis. However, the overall percentage decrease in the plasma level of atrial natriuretic peptide (43.6 ± 7.5%) after dialysis was significantly greater than that observed for brain natriuretic peptide (15.9 ± 5.3%, P<0.005). 5. Displacement curves of iodinated atrial natriuretic peptide from bovine adrenal membranes by human atrial natriuretic peptide (99–126) and human brain natriuretic peptide (1–32) gave a median inhibitory concentration of 144 pmol/l for atrial natriuretic peptide and 724.4 pmol/l for brain natriuretic peptide. The cross-reactivity of human brain natriuretic peptide with the atrial natriuretic peptide receptor preparation was 19.5% of that of atrial natriuretic peptide, indicating that human brain natriuretic peptide has a lower binding affinity for the atrial natriuretic peptide receptor/binding site on bovine adrenal membranes. 6. These results suggest that brain natriuretic peptide is co-secreted with atrial natriuretic peptide and may also be an important factor in the adaptive mechanisms to impairment of renal function. However, whether brain natriuretic peptide has an independent and fundamentally important role in man remains to be investigated.


1986 ◽  
Vol 110 (2) ◽  
pp. 193-196 ◽  
Author(s):  
J. V. Anderson ◽  
A. E. G. Raine ◽  
A. Proudler ◽  
S. R. Bloom

ABSTRACT Twenty patients with chronic renal failure were studied before and after haemodialysis. Plasma atrial natriuretic peptide (ANP) concentrations were markedly elevated (P < 0·01) before dialysis in comparison with healthy control subjects. After haemodialysis the plasma ANP concentration was lower in 19 patients (P < 0·01) but remained above the normal range in all but three cases. Systolic and diastolic blood pressure and body weight fell during dialysis but none of these changes correlated with the reduction of the plasma ANP concentration. Chromatographic analysis of plasma extracts indicated that α-ANP is the predominant circulating molecular form. The increase in concentration of ANP in plasma between dialyses, at a time when many patients are susceptible to sodium and water overload, and its return towards normal after dialysis supports the putative role of ANP as a circulating factor released in response to sodium and water accumulation. J. Endocr. (1986) 110, 193–196


1988 ◽  
Vol 75 (3) ◽  
pp. 243-249 ◽  
Author(s):  
Stanislas Czekalski ◽  
Catherine Michel ◽  
Jean-Claude Dussaule ◽  
Philippe Touraine ◽  
Francoise Mignon ◽  
...  

1. In order to examine the potential role of endogenous atrial natriuretic peptide (ANP) in modulating the increased sodium excretion per nephron in chronic renal failure, we studied healthy subjects with normal renal function (group I) and patients with moderate (group II) or severe chronic renal failure (group III) before, during and after administration of an intravenous sodium load. All subjects had been on a controlled diet containing 120 mmol of sodium per day for 5 days before the study. 2. Under basal conditions, plasma ANP and fractional excretion of sodium (FENa) were highest in group III. Both parameters increased in response to the sodium load in the three groups studied (P < 0.001). Changes with time differed from group to group (P < 0.05), the more marked response for both parameters being observed in group III. After adjustment with respect to plasma ANP (analysis of covariance), FENa was no longer modified in response to the sodium load, whereas adjustment of FENa with respect to mean blood pressure was without consequence on the significance of its change with time. This demonstrates that plasma ANP, but not mean blood pressure, represents the main factor producing variation in FENa during and after the sodium load. 3. These results suggest an important role for plasma ANP in promoting adaptation of short-term sodium excretion in response to an acute sodium load in patients with chronic renal failure who ingest a normal sodium intake.


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