High atrial natriuretic peptide, endothelin and neutral endopeptidase in the pericardial fluid of cardiac patients

Two natriuretic peptides, atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP), are found principally in the heart. In preliminary experiments with mouse kidney cells or slices, we found mouse BNP1-45 much more potent than ANP1-28 in causing elevations of cGMP (>50-fold). The guanylyl cyclase-A (GC-A) receptor has been suggested to represent the primary means by which both peptides signal. In cultured cells overexpressing GC-A, BNP and ANP were almost equivalent in potency, suggesting that a receptor unique for BNP exists in the kidney. However, in mice lacking the GC-A gene, neither BNP nor ANP significantly elevated cGMP in kidney slices. Phosphoramidon, a neutral endopeptidase inhibitor, shifted the apparent potency of ANP to values equivalent to that of BNP, suggesting these kidney cell/slices rapidly degrade ANP but not BNP. Mass spectroscopic analysis confirmed that ANP is rapidly cleaved at the first cysteine of the disulfide ring, whereas BNP is particularly stable to such cleavage. Other tissues (heart, aorta) failed to significantly degrade ANP or BNP, and therefore the kidney-specific degradation of ANP provides a mechanism for preferential regulation of kidney function by BNP independent of peripheral ANP concentration.Key words: guanylyl cyclase-A, atrial natriuretic peptide, B-type natriuretic peptide, neutral endopeptidase.

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Neutral Endopeptidase Inhibitors and Atrial Natriuretic Peptide

The Journal of Clinical Pharmacology ◽

10.1002/j.1552-4604.1991.tb03773.x ◽

1991 ◽

Vol 31 (8) ◽

pp. 758-762 ◽

Cited By ~ 5

Author(s):

Godfrey Achilihu ◽

William H. Frishman ◽

Andre Landau

Keyword(s):

Atrial Natriuretic Peptide ◽

Natriuretic Peptide ◽

Neutral Endopeptidase ◽

Atrial Natriuretic

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

Clinical Science ◽

10.1042/cs0950547 ◽

1998 ◽

Vol 95 (5) ◽

pp. 547-555 ◽

Cited By ~ 21

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.

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