AJP - Heart Watch the video to see how APS reaches out to developing nations.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Heart Circ Physiol 273: H2372-H2379, 1997;
0363-6135/97 $5.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Rademaker, M. T.
Right arrow Articles by Richards, A. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Rademaker, M. T.
Right arrow Articles by Richards, A. M.
Vol. 273, Issue 5, H2372-H2379, November 1997

Clearance receptors and endopeptidase: equal role in natriuretic peptide metabolism in heart failure

Miriam Tessa Rademaker1, Christopher John Charles1, Teddy Kosoglou2, Andrew A. Protter3, Eric Arnold Espiner1, Michael Gary Nicholls1, and Arthur Mark Richards1

1 Department of Medicine, The Christchurch School of Medicine, Christchurch, New Zealand; 2 Schering-Plough Research Institute, Kenilworth, New Jersey 07033-0539; and 3 Scios, Mountain View, California 94043

The effects of separate and combined endopeptidase inhibition (by SCH-32615) and natriuretic peptide receptor C blockade [by C-ANP-(4---23)] on the clearance and bioactivity of atrial (ANP) and brain (BNP) natriuretic peptides was investigated in eight sheep with heart failure. SCH-32615 and C-ANP-(4---23) administered separately induced significant and proportionate dose-dependent rises in plasma ANP, BNP, and guanosine 3',5'-cyclic monophosphate (cGMP) levels. Associated with these changes were reductions in arterial pressure, left atrial pressure, and peripheral resistance and increases in cardiac output, urine volume, sodium excretion, and creatinine clearance. SCH-32615 induced greater diuresis and natriuresis than C-ANP-(4---23). Combined administration of SCH-32615 and C-ANP-(4---23) induced greater than additive rises in plasma ANP, BNP, and cGMP concentrations, with enhanced hemodynamic effects, diuresis, and natriuresis and reduced plasma aldosterone levels. In conclusion, we find that the enzymatic and receptor clearance pathways contribute equally to the metabolism of endogenous ANP and BNP in sheep with heart failure. Combined inhibition of both degradative pathways was associated with enhanced hormonal, hemodynamic, and renal effects and may have greater potential therapeutic value than either agent separately.

guanosine 3',5'-cyclic monophosphate; ventricular pacing; hemodynamics; natriuresis


This article has been cited by other articles:


Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
T. E. H. Christoffersen, M. Aplin, C. C. Strom, S. P. Sheikh, O. Skott, P. K. Busk, S. Haunso, and L. B. Nielsen
Increased natriuretic peptide receptor A and C gene expression in rats with pressure-overload cardiac hypertrophy
Am J Physiol Heart Circ Physiol, April 1, 2006; 290(4): H1635 - H1641.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
M. Schou, M. K. Dalsgaard, O. Clemmesen, E. A. Dawson, C. C. Yoshiga, H. B. Nielsen, F. Gustafsson, P. R. Hildebrandt, and N. H. Secher
Kidneys extract BNP and NT-proBNP in healthy young men
J Appl Physiol, November 1, 2005; 99(5): 1676 - 1680.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
R. Almirez and A. A. Protter
Clearance of Human Brain Natriuretic Peptide in Rabbits; Effect of the Kidney, the Natriuretic Peptide Clearance Receptor, and Peptidase Activity
J. Pharmacol. Exp. Ther., May 1, 1999; 289(2): 976 - 980.
[Abstract] [Full Text]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
C. J. Pemberton, T. G. Yandle, M. T. Rademaker, C. J. Charles, G. D. Aitken, and E. A. Espiner
Amino-terminal proBNP in ovine plasma: evidence for enhanced secretion in response to cardiac overload
Am J Physiol Heart Circ Physiol, October 1, 1998; 275(4): H1200 - H1208.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online