Document Detail

Endothelin acts as a paracrine regulator of stretch-induced atrial natriuretic peptide release.
MedLine Citation:
PMID:  7503296     Owner:  NLM     Status:  MEDLINE    
Several lines of evidence suggest a paracrine regulatory role for endothelin (ET) in the release of atrial natriuretic peptide (ANP). To investigate this possibility, we used the ET A-type receptor (ETA-R) competitive inhibitor cyclo(D-Asp-Pro-D-Val-Leu-D-Trp) (BQ-123) in isolated perfused atria to determine the effect of endogenously produced ET on the release of ANP. Initially, we found that high pressure (8-10 mmHg) increased the mean ANP secretion rate by 117.3 +/- 21.2% (P < 0.05). Next, we found that at high pressure 50 nM of exogenously applied ET significantly augmented the stretch-induced release of ANP (P < 0.05) and that this response could be significantly attenuated in a dose-dependent manner by 1 and 3 microM BQ-123 (P < 0.05). These experiments proved the efficacy of the inhibitor in our model. Subsequently, we found that the stretch-induced release of ANP was significantly reduced to 51.5 +/- 13.0 and 22.3 +/- 11.8% by 1 and 3 microM BQ-123, respectively (P < 0.05). Because the perfused atria model eliminates systemic cardiovascular effects, allows control and direct recording of the intra-atrial pressure, and preserves the potential endothelium-myocyte control system, we conclude that the stretch-induced release of ANP is partially regulated by ET and that the ET is locally produced and constitutes a paracrine control system.
J P Skvorak; S J Nazian; J R Dietz
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The American journal of physiology     Volume:  269     ISSN:  0002-9513     ISO Abbreviation:  Am. J. Physiol.     Publication Date:  1995 Nov 
Date Detail:
Created Date:  1996-01-17     Completed Date:  1996-01-17     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0370511     Medline TA:  Am J Physiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  R1093-8     Citation Subset:  IM    
Department of Physiology and Biophysics, University of South Florida College of Medicine, Tampa 33612, USA.
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MeSH Terms
Atrial Function* / drug effects
Atrial Natriuretic Factor / metabolism*
Endothelins / pharmacology,  physiology*
Myocardium / metabolism*
Osmolar Concentration
Peptides, Cyclic / pharmacology
Physical Stimulation
Rats, Sprague-Dawley
Receptors, Endothelin / antagonists & inhibitors
Grant Support
44868//PHS HHS
Reg. No./Substance:
0/Endothelins; 0/Peptides, Cyclic; 0/Receptors, Endothelin; 136553-81-6/cyclo(Trp-Asp-Pro-Val-Leu); 85637-73-6/Atrial Natriuretic Factor

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