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.
Calcineurin–Nuclear Factor of Activated T Cells Pathway–Dependent Cardiac Remodeling in Mice Deficient in Guanylyl Cyclase A, a Receptor for Atrial and Brain Natriuretic Peptides
