PMID- 11082129
OWN - NLM
STAT- MEDLINE
DCOM- 20010202
LR  - 20181113
IS  - 0007-1188 (Print)
IS  - 0007-1188 (Linking)
VI  - 131
IP  - 6
DP  - 2000 Nov
TI  - Effect of neutral endopeptidase inhibitor on endogenous atrial natriuretic 
      peptide as a paracrine factor in cultured cardiac fibroblasts.
PG  - 1204-10
AB  - 1. Cardiac remodelling is a fundamental response to hypertension, myocardial 
      infarction and chronic heart failure, and involves cardiac fibroblast 
      proliferation and production of extracellular matrix components such as collagen. 
      The present study was performed to examine the role of endogenous atrial 
      natriuretic peptide (ANP) as a possible paracrine factor for cardiac fibroblasts, 
      and to examine the effects of three neutral endopeptidase (NEP) inhibitors, 
      thiorphan, phosphoramidon and ONO-BB-039-02 (ONO-BB) on endogenous ANP-induced 
      changes in collagen synthesis by cultured neonatal rat cardiac fibroblasts. 2. 
      Each NEP inhibitor singly had no significant effect on collagen synthesis by 
      cardiac fibroblasts, except for maximum concentration (10(-3) M) of thiorphan. 3. 
      Exogenous ANP inhibited collagen synthesis in a concentration-dependent manner 
      (10(-8) - 10(-6) M). Thiorphan (10(-4) and 10(-3) M) and phosphoramidon (10(-5) 
      and 10(-4) M) enhanced the ANP (10(-7) M)-induced decrease in collagen synthesis. 
      ONO-BB (10(-5) and 10(-4) M) slightly enhanced the ANP-induced decrease in 
      collagen synthesis. 4. Myocyte-conditioned medium (MC-CM), as well as exogenous 
      ANP, inhibited collagen synthesis dose-dependently. The decrease in collagen 
      synthesis at 100% MC-CM was augmented by thiorphan (10(-3) M), phosphoramidon 
      (10(-4) M) and ONO-BB (10(-4) M). 5. HS-142-1, a natriuretic peptide receptor 
      antagonist, significantly reduced the MC-CM plus thiorphan- and MC-CM plus 
      ONO-BB-induced decrease in collagen synthesis, by 92 and 62%, respectively and 
      showed a tendency to attenuate the MC-CM plus phosphoramidon-induced decrease in 
      collagen synthesis by 40%. 6. Our observations suggested that endogenous ANP 
      released from cardiomyocytes inhibited collagen synthesis as a paracrine factor 
      and that NEP inhibitors enhanced the activity of this peptide in cardiac 
      fibroblasts.
FAU - Maki, T
AU  - Maki T
AD  - Research Institute, National Cardiovascular Center, 5-7-1, Fujishirodai, Suita, 
      Osaka 565-8565, Japan.
FAU - Horio, T
AU  - Horio T
FAU - Yoshihara, F
AU  - Yoshihara F
FAU - Suga, S
AU  - Suga S
FAU - Takeo, S
AU  - Takeo S
FAU - Matsuo, H
AU  - Matsuo H
FAU - Kangawa, K
AU  - Kangawa K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Protease Inhibitors)
RN  - 85637-73-6 (Atrial Natriuretic Factor)
RN  - 9007-34-5 (Collagen)
RN  - EC 3.4.24.11 (Neprilysin)
SB  - IM
MH  - Animals
MH  - Atrial Natriuretic Factor/*drug effects/pharmacology/physiology
MH  - Cells, Cultured
MH  - Collagen/biosynthesis/*drug effects
MH  - Culture Media, Conditioned/pharmacology
MH  - Fibroblasts/*drug effects/physiology
MH  - Heart Ventricles/cytology/drug effects
MH  - Neprilysin/*antagonists & inhibitors
MH  - Paracrine Communication/*drug effects/physiology
MH  - Protease Inhibitors/*pharmacology
MH  - Rats
MH  - Rats, Wistar
MH  - Ventricular Function
PMC - PMC1572435
EDAT- 2000/11/18 11:00
MHDA- 2001/03/03 10:01
PMCR- 2001/11/01
CRDT- 2000/11/18 11:00
PHST- 2000/11/18 11:00 [pubmed]
PHST- 2001/03/03 10:01 [medline]
PHST- 2000/11/18 11:00 [entrez]
PHST- 2001/11/01 00:00 [pmc-release]
AID - 0703679 [pii]
AID - 10.1038/sj.bjp.0703679 [doi]
PST - ppublish
SO  - Br J Pharmacol. 2000 Nov;131(6):1204-10. doi: 10.1038/sj.bjp.0703679.