Regional plasma levels of cardiac peptides and their response to acute neutral endopeptidase inhibition in man

1998 ◽  
Vol 95 (5) ◽  
pp. 547-555 ◽  
Author(s):  
J. G. LAINCHBURY ◽  
M. G. NICHOLLS ◽  
E. A. ESPINER ◽  
H. IKRAM ◽  
T. G. YANDLE ◽  
...  
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Brain Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Coronary Sinus ◽  
Femoral Artery ◽  
Natriuretic Peptides ◽  
Plasma Levels ◽  
Neutral Endopeptidase ◽  
Brain Natriuretic Peptides ◽  
Atrial Natriuretic

1.The cardiac natriuretic peptides, atrial natriuretic peptide and brain natriuretic peptide, are degraded via clearance receptors and the enzyme neutral endopeptidase (EC 3.4.24.11). We studied the regional plasma concentrations of these peptides and their response to acute neutral endopeptidase inhibition in a consecutive series of patients with a broad spectrum of severity of cardiac dysfunction who were undergoing diagnostic right and left heart catheterization (24 patients, mean age 62.6 years). 2.Baseline blood samples were obtained for hormone analysis from femoral artery, femoral vein, renal vein, hepatic vein, superior vena cava, coronary sinus and pulmonary artery, and initial haemodynamic measurements were made. Twelve patients then received a neutral endopeptidase inhibitor (SCH 32615, 200 ;mg intravenously) and 12 received vehicle alone. The cardiac catheterization procedure was then completed and haemodynamic and hormone measurements were repeated. 3.Haemodynamic status was similar at baseline in both groups, and at repeated measurement (post-procedure after placebo or active drugs) haemodynamic variables were not significantly different from baseline values. Plasma levels of atrial and brain natriuretic peptides exhibited an arteriovenous increment (344% and 124% respectively) across the heart (femoral artery to coronary sinus) and decrement (by 28–54% and 9–16% respectively) across all other tissue beds (P< 0.05 for all) except the lung (no change). Final levels of atrial natriuretic peptide rose above initial levels at all sites in both groups (P< 0.05) except coronary sinus levels in the vehicle group (no change). The increase was consistently greater in the inhibitor group at all sites (P< 0.05 versus placebo). Levels of brain natriuretic peptide rose at all sites in the inhibitor group only (P< 0.05). The transcardiac step-up in atrial natriuretic peptide was markedly augmented after the administration of neutral endopeptidase inhibitor. Other tissue gradients were not significantly altered by neutral endopeptidase inhibitor. 4.Atrial and brain natriuretic peptides in plasma are degraded by a number of tissues, and respond differently to cardiac catheterization. Neutral endopeptidase has a significant role in determining plasma levels of natriuretic peptides, in part perhaps by influencing the amount of intact peptide reaching the circulation after secretion from the heart.

Increased Secretion of Atrial and Brain Natriuretic Peptides during Acute Myocardial Ischaemia Induced by Dynamic Exercise in Patients with Angina Pectoris

1995 ◽  
Vol 88 (5) ◽  
pp. 551-556 ◽  
Author(s):  
Kazumasa Marumoto ◽  
Mareomi Hamada ◽  
Kunio Hiwada
Keyword(s):  
Angina Pectoris ◽  
Atrial Natriuretic Peptide ◽  
Brain Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Natriuretic Peptides ◽  
Plasma Levels ◽  
Dynamic Exercise ◽  
Peak Exercise ◽  
Control Group ◽  
Brain Natriuretic Peptides

1. This study was conducted to assess the role of atrial and brain natriuretic peptides during acute myocardial ischaemia associated with dynamic exercise. 2. Study subjects consisted of 35 angiographically proven patients with angina pectoris and 35 angiographically normal control subjects. All subjects underwent 201Tl dynamic exercise testing. The presence and localization of the exercise-induced acute myocardial perfusion defect were assessed by 201Tl single-photon emission computed tomography. The severity score was calculated using the early image for quantitative assessment of the acute myocardial perfusion defect. 3. Plasma levels of atrial natriuretic peptide increased from 21.3 ± 3.8 to 72.2 ± 26.7 pg/ml (P < 0.01) in the angina pectoris group, and increased from 19.4 ± 2.4 to 36.4 ± 17.4 pg/ml (P < 0.01) in the control group during dynamic exercise. Plasma levels of brain natriuretic peptide increased from 2.8 ± 0.8 to 6.9 ± 2.6 pg/ml (P < 0.01) in the angina pectoris group, but did not change significantly in the control group (from 2.7 ± 0.7 to 2.9 ± 1.0 pg/ml) during dynamic exercise. At peak exercise, plasma levels of these natriuretic peptides in the angina pectoris group were significantly higher than those in the control group (P < 0.01). 4. At peak exercise, there were correlations between the plasma level of atrial natriuretic peptide and heart rate in both the angina pectoris and control groups (P < 0.01, r = 0.46; P < 0.01, r = 0.51, respectively), but no significant correlations between the plasma level of brain natriuretic peptide and heart rate in either group. The plasma levels of these peptides at peak exercise correlated well with the severity score in the angina pectoris group (atrial natriuretic peptide, r = 0.71, P < 0.01; brain natriuretic peptide, r = 0.69, P < 0.01). 5. The present study showed that plasma levels of atrial and brain natriuretic peptides significantly increased during acute myocardial ischaemia associated with dynamic exercise.

Increased Plasma Levels of Adrenomedullin in Patients with Hypertrophic Cardiomyopathy: Its Relation to Endothelin-1, Natriuretic Peptides and Noradrenaline

1998 ◽  
Vol 94 (1) ◽  
pp. 21-28 ◽  
Author(s):  
Mareomi Hamada ◽  
Yuji Shigematsu ◽  
Hideo Kawakami ◽  
Naoto Minamino ◽  
Kenji Kangawa ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Atrial Natriuretic Peptide ◽  
Brain Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Natriuretic Peptides ◽  
Plasma Levels ◽  
Endothelin 1 ◽  
Brain Natriuretic Peptides ◽  
Significant Difference ◽  
Normal Controls

1. The aim of this study was to elucidate the pathophysiological role of adrenomedullin and the relation between adrenomedullin and other hormones in patients with hypertrophic cardiomyopathy. 2. Fourteen patients with hypertrophic obstructive cardiomyopathy (HOCM), 26 patients with hypertrophic non-obstructive cardiomyopathy (HNCM) and 14 normal control subjects participated in this study. Radioimmunoassay for plasma adrenomedullin concentration was performed with adrenomedullin-M antibody. Plasma levels of endothelin-1, atrial and brain natriuretic peptides and noradrenaline were also measured. 3. Plasma levels of adrenomedullin were higher in patients with hypertrophic cardiomyopathy (8.43 ± 3.73 pmol/l) than in normal controls (5.24 ± 0.44 pmol/l, P < 0.005). There was no significant difference between HOCM and HNCM patients. There was a weak correlation between plasma levels of adrenomedullin and total 12-lead QRS voltage in patients with hypertrophic cardiomyopathy (r = 0323, P < 0.05) 4. Plasma levels of endothelin-1, atrial and brain natriuretic peptides were higher in hypertrophic cardiomyopathy than in normal controls. Endothelin-1 showed no significant difference between HOCM and HNCM patients, but atrial and brain natriuretic peptides were higher in HOCM than in HNCM patients. There was a positive correlation between plasma levels of adrenomedullin and endothelin-1 (r = 0.575, P < 0.0001), but no correlation between plasma levels of adrenomedullin and atrial natriuretic peptide, brain natriuretic peptide and noradrenaline. 5. Our results indicate that adrenomedullin may play an important role to maintain haemodynamics in patients with hypertrophic cardiomyopathy, and its action may be related to endothelin-1 but independent of atrial natriuretic peptide, brain natriuretic peptide and noradrenaline.

Elevated levels of brain natriuretic peptide in acute hypoxaemic chronic obstructive pulmonary disease

1992 ◽  
Vol 83 (5) ◽  
pp. 529-533 ◽  
Author(s):  
Chim C. Lang ◽  
Wendy J. Coutie ◽  
Allan D. Struthers ◽  
D. Paul Dhillon ◽  
John H. Winter ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Atrial Natriuretic Peptide ◽  
Brain Natriuretic Peptide ◽  
Pulmonary Disease ◽  
Natriuretic Peptide ◽  
Plasma Levels ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Arterial Partial Pressure ◽  
Atrial Natriuretic

1. Studies in vitro have recently shown that both atrial natriuretic peptide and brain natriuretic peptide have pulmonary vasorelaxant activity. The purpose of the present study was to evaluate for the first time whether plasma levels of brain natriuretic peptide are elevated in chronic obstructive pulmonary disease. Plasma levels of brain natriuretic peptide and atrial natriuretic peptide were therefore measured in 12 patients admitted with acute hypoxaemic chronic obstructive pulmonary disease [arterial partial pressure of O2, 6.2 ± 0.4 kPa; arterial partial pressure of CO2, 6.9 ± 0.1 kPa; forced expiratory volume in 1 s, 0.6 ± 0.07 litre (27 ± 3% of predicted)]. All but three patients had oedema on admission. 2. Plasma levels of both brain natriuretic peptide and atrial natriuretic peptide were elevated in patients with chronic obstructive pulmonary disease (31.4 ± 4.1 pmol/l and 45.0 ± 8.1 pmol/l, respectively) compared with healthy control subjects (1.7 ± 0.8 pmol/l and 8.0 ± 3.5 pmol/l, respectively). Thus, plasma levels of brain natriuretic peptide and atrial natriuretic peptide in patients with chronic obstructive pulmonary disease were increased by 18.5- and 5.6-fold respectively compared with healthy control subjects. 3. There was a significant inverse correlation between the plasma level of brain natriuretic peptide and the arterial partial pressure of O2 (r = −0.65, r2 = 0.42, P = 0.03), but not between the plasma atrial natriuretic peptide level and the arterial partial pressure of O2 (r2 = 0.07, not significant). The arterial partial pressure of CO2 did not correlate with the plasma level of either brain natriuretic peptide or atrial natriuretic peptide. 4. Thus, plasma levels of brain natriuretic peptide were proportionately higher than those of atrial natriuretic peptide in patients with hypoxaemic chronic obstructive pulmonary disease. Unlike those of atrial natriuretic peptide, plasma levels of brain natriuretic peptide were correlated with the degree of hypoxaemia. Further studies are required to investigate the release and clearance of brain natriuretic peptide in chronic obstructive pulmonary disease, as well as its pulmonary vasodilator activity in vivo.

Adrenal receptors for natriuretic peptides and inhibition of aldosterone secretion in calf zona glomerulosa cells in culture

1993 ◽  
Vol 129 (1) ◽  
pp. 59-64 ◽  
Author(s):  
Eduardo N Cozza ◽  
Mark F Foecking ◽  
Maria del Carmen Vila ◽  
Celso E Gomez-Sanchez
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Brain Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Natriuretic Peptides ◽  
Peptide Binding ◽  
Main Band ◽  
Aldosterone Production ◽  
Glomerulosa Cells ◽  
Stimulation Of ◽  
Atrial Natriuretic

Atrial and brain natriuretic peptides specifically bind to primary cultures of calf adrenal glomerulosa cells. Binding of both natriuretic peptides to the same receptor has been proved by: a Dixon plot showing competitive effects for the binding of 125I-labeled brain natriuretic peptide in the presence of increasing concentrations of unlabeled atrial natriuretic peptide; a Scatchard plot showing a lower dissociation constant (Kd) for atrial natriuretic peptide than for brain natriuretic peptide binding, but the maximum binding (Bmax) values were the same; autoradiography of sodium dodecyl sulfate polyacrylamide gels after cross-linking of 125I-labeled atrial natriuretic peptide and 125I-labeled brain natriuretic peptide, showing the same molecular weights for both peptide receptors—a single 66-kD band in whole cells and a main band at 125 kD in membranes. C-Type atrial natriuretic peptide only slightly displaced atrial natriuretic peptide binding. Angiotensin II- and potassium-mediated stimulation of aldosterone production were inhibited strongly and to the same degree by atrial and brain natriuretic peptide but only slightly by C-type atrial natriuretic peptide. Stimulation of aldosterone production mediated by adrenocorticotropin was only partially inhibited by atrial and brain natriuretic peptide, while baseline aldosterone was not affected. These results suggest that atrial and brain natriuretic peptide bind to the same receptors and provoke the same effects on aldosterone production. The weak effects found with C-type atrial natriuretic peptide suggest that the primary culture of calf adrenal glomerulosa cells contain the guanylate cyclase A receptor.

Release of atrial natriuretic peptide by atrial distension

1985 ◽  
Vol 63 (6) ◽  
pp. 739-742 ◽  
Author(s):  
J. R. Ledsome ◽  
N. Wilson ◽  
C. A. Courneya ◽  
A. J. Rankin
Keyword(s):  
Heart Rate ◽  
Atrial Natriuretic Peptide ◽  
Pulmonary Vein ◽  
Natriuretic Peptide ◽  
Coronary Sinus ◽  
Femoral Artery ◽  
Left Atrial ◽  
Cervical Vagotomy ◽  
Atrial Receptors ◽  
Atrial Natriuretic

A heterologous radioimmunoassay was used to measure the concentration of immunoreactive atrial natriuretic peptide (iANP) in plasma from the femoral artery of eight chloralose anaesthetized dogs. Mitral obstruction which increased left atrial pressure by 11 cmH2O increased plasma iANP from 97 ± 10.3 (mean ± SE) to 135 ± 14.3 pg/mL. Pulmonary vein distension increased heart rate but did not increase plasma iANP. Bilateral cervical vagotomy and administration of atenolol (2 mg/kg) did not prevent the increase in iANP with mitral obstruction. Samples of blood from the coronary sinus had plasma iANP significantly higher than simultaneous samples from the femoral artery confirming the cardiac origin of the iANP. Release of iANP depends on direct stretch of the atrium rather than on a reflex involving left atrial receptors.

Changes in the plasma levels of atrial natriuretic peptides during mineralocorticoid escape in man

1987 ◽  
Vol 72 (5) ◽  
pp. 531-539 ◽  
Author(s):  
Francesco P. Cappuccio ◽  
Nirmala D. Markandu ◽  
Martin G. Buckley ◽  
Giuseppe A. Sagnella ◽  
Angela C. Shore ◽  
...  
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Healthy Volunteers ◽  
Natriuretic Peptide ◽  
Natriuretic Peptides ◽  
Plasma Levels ◽  
Sodium Intake ◽  
Atrial Natriuretic Peptides ◽  
Atrial Natriuretic

1. Plasma levels of atrial natriuretic peptide (ANP) were measured by radioimmunoassay in eight normal healthy volunteers before and during mineralocorticoid escape. 2. Mean plasma ANP on a fixed sodium intake before fludrocortisone was 6.5± sem 1.1 pg/ml. Within 24 h of fludrocortisone administration there was a significant increase in plasma ANP which continued to increase daily reaching a plateau by day 4 (14.9 ± 2.4 pg/ml) to day 7 (15.1 ± 2.6 pg/ml). 3. The rise in plasma ANP was closely related to the amount of sodium retained during the fludrocortisone treatment and the sodium ‘escape’ occurred by days 4 to 7. 4. These results support the concept that ANP could play an important hormonal role in overcoming the sodium-retaining effects of mineralocorticoids in man.

Clearance of brain natriuretic peptide in patients with chronic heart failure: indirect evidence for a neutral endopeptidase mechanism but against an atrial natriuretic peptide clearance receptor mechanism

1992 ◽  
Vol 82 (6) ◽  
pp. 619-623 ◽  
Author(s):  
Chim C. Lang ◽  
Joseph G. Motwani ◽  
Wendy J. R. Coutie ◽  
Allan D. Struthers
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Atrial Natriuretic Peptide ◽  
Human Brain ◽  
Brain Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Neutral Endopeptidase ◽  
Striking Similarity ◽  
Plasma Atrial Natriuretic Peptide ◽  
Atrial Natriuretic

1. Brain natriuretic peptide is a new natriuretic hormone with striking similarity to atrial natriuretic peptide, but there are no previous data concerning its clearance in man. Two pathways of clearance for atrial natriuretic peptide are recognized: degradation by neutral endopeptidase and binding to atrial natriuretic peptide clearance receptors. We have examined the effect of candoxatril, an inhibitor of neutral endopeptidase (dose range 10–200 mg), and the effect of an infusion of a pharmacological dose [45 μg (90 μg in two patients)] of synthetic human atrial natriuretic peptide on plasma human brain natriuretic peptide-like immunoreactivity levels in seven patients with mild to moderate chronic heart failure. 2. Plasma human brain natriuretic peptide-like immunoreactivity levels were elevated in all patients (mean ± sem 22.0 ± 6.2 pmol/l) compared with healthy control subjects (1.3 ± 0.2 pmol/l, n = 11). 3. In all patients, candoxatril increased both plasma atrial natriuretic peptide (P < 0.05) and plasma human brain natriuretic peptide-like immunoreactivity (P < 0.05) levels. 4. By contrast, an exogenous infusion of atrial natriuretic peptide had no effect on plasma human brain natriuretic peptide-like immunoreactivity levels despite increasing the plasma atrial natriuretic peptide concentration to 424 ± 74 pmol/l, which is a level of atrial natriuretic peptide which would have ‘swamped’ all atrial natriuretic peptide clearance receptors. 5. We have therefore shown that plasma human brain natriuretic peptide-like immunoreactivity levels in chronic heart failure are increased by a neutral endopeptidase inhibitor, but are unchanged by an exogenous infusion of atrial natriuretic peptide. Our results suggest that in patients with chronic heart failure, degradation by neutral endopeptidase is an important pathway for clearance of brain natriuretic peptide. By an indirect approach, we did not find any evidence of a role for atrial natriuretic peptide clearance receptors in the metabolism of brain natriuretic peptide in these patients. Although this is in agreement with work in vitro, there could be alternative explanations for the lack of a change in circulating human brain natriuretic peptide-like immunoreactivity during exogenous administration of atrial natriuretic peptide.

Atrial natriuretic peptide in eel plasma, heart and brain characterized by homologous radioimmunoassay

1992 ◽  
Vol 135 (2) ◽  
pp. 325-331 ◽  
Author(s):  
Y. Takei ◽  
K. Ando ◽  
M. Kawakami
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Natriuretic Peptides ◽  
High Performance ◽  
Molecular Form ◽  
High Sensitivity ◽  
Molecular Forms ◽  
Brain Natriuretic Peptides ◽  
The Brain ◽  
Atrial Natriuretic

ABSTRACT A highly specific and sensitive radioimmunoassay has been developed for the measurement of eel atrial natriuretic peptide (ANP). The antiserum, raised against eel ANP-(1–27) did not cross-react with two other eel natriuretic peptides, i.e. eel ventricular natriuretic peptide and C-type natriuretic peptide (CNP), or with any mammalian ANPs, CNPs or brain natriuretic peptides so far identified. The minimal detectable amount was 0·39 fmol (0·90 pg)/tube with more than 99% confidence. Because of its high sensitivity, the radioimmunoassay makes it possible to measure eel ANP directly with only a few microlitres of plasma without extraction. Using the radioimmunoassay we found high levels of ANP in the atrium (11 ± 2 pmol/mg wet tissue, n = 8), and much lower levels in the ventricle (56 ±8 fmol/mg, n=8) and the brain (22±1 fmol/mg, n = 8) of eels. Eel plasma contained a large amount of ANP (247 ± 66 fmol/ml, n= 8) compared with the levels reported in mammals, although atrial levels are similar between eels and mammals. Gel-permeation chromography revealed that a major form of ANP stored in the eel atrium, ventricle and brain has a molecular mass of approximately 14 kDa but low molecular forms of about 3 kDa are predominant in eel plasma. A detailed analysis with reverse-phase high-performance liquid chromatography showed that a major molecular form circulating in eel plasma is ANP-(1–27). ANP-(1–27) was also detected in small amounts in the eel atrium, ventricle and brain. Journal of Endocrinology (1992) 135, 325–331

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