Document Detail

Natriuretic peptide receptor-C regulates coronary blood flow and prevents myocardial ischemia/reperfusion injury: novel cardioprotective role for endothelium-derived C-type natriuretic peptide.
MedLine Citation:
PMID:  15337698     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Ischemia/reperfusion (I/R) injury complicates myocardial infarction and stroke by exacerbating tissue damage and increasing risk of mortality. We have recently identified C-type natriuretic peptide (CNP) as an endothelium-derived hyperpolarizing factor in the mesenteric resistance vasculature and described a novel signaling pathway involving activation of natriuretic peptide receptor C (NPR-C), which plays a pivotal role in the regulation of local blood flow. We tested the hypothesis that CNP/NPR-C signaling is a novel regulatory pathway governing coronary blood flow and protecting against I/R injury. METHODS AND RESULTS: CNP and (Cys18)-atrial natriuretic factor (4-23) amide (cANF(4-23)) elicited dose-dependent decreases in coronary perfusion pressure (CPP) that were blocked by Ba(2+) and ouabain in the isolated Langendorff rat heart. The endothelium-dependent vasodilator acetylcholine elicited the release of CNP from the coronary endothelium. CNP and cANF(4-23) reduced infarct size after 25 minutes of global ischemia and 120 minutes of reperfusion, maintaining CPP and left ventricular pressure at preischemic values. The vasorelaxant and protective activity of CNP and cANF(4-23) were enhanced in the absence of endothelium-derived nitric oxide. CONCLUSIONS: Endothelium-derived CNP is involved in the regulation of the coronary circulation, and NPR-C activation underlies the vasorelaxant activity of this peptide. Moreover, this newly defined pathway represents a protective mechanism against I/R injury and a novel target for therapeutic intervention in ischemic cardiovascular disorders.
Adrian Hobbs; Paul Foster; Craig Prescott; Ramona Scotland; Amrita Ahluwalia
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2004-08-30
Journal Detail:
Title:  Circulation     Volume:  110     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2004 Sep 
Date Detail:
Created Date:  2004-09-08     Completed Date:  2006-04-07     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1231-5     Citation Subset:  AIM; IM    
Wolfson Institute for Biomedical Research, London, UK.
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MeSH Terms
Acetylcholine / pharmacology
Atrial Natriuretic Factor / pharmacology,  therapeutic use
Barium / pharmacology
Coronary Circulation / drug effects*
Drug Evaluation, Preclinical
Endothelium, Vascular / drug effects,  secretion
Myocardial Infarction / drug therapy,  pathology
Myocardial Reperfusion Injury / prevention & control
NG-Nitroarginine Methyl Ester / pharmacology
Natriuretic Peptide, C-Type / pharmacology,  physiology*,  secretion,  therapeutic use
Nitric Oxide / physiology
Ouabain / pharmacology
Peptide Fragments / pharmacology,  therapeutic use
Rats, Wistar
Receptors, Atrial Natriuretic Factor / drug effects,  physiology*
Signal Transduction
Vasodilation / drug effects
Vasodilator Agents / pharmacology,  therapeutic use
Reg. No./Substance:
0/(Cys18)-atrial natriuretic factor (4-23)-amide; 0/Peptide Fragments; 0/Vasodilator Agents; 10102-43-9/Nitric Oxide; 127869-51-6/Natriuretic Peptide, C-Type; 50903-99-6/NG-Nitroarginine Methyl Ester; 51-84-3/Acetylcholine; 630-60-4/Ouabain; 7440-39-3/Barium; 85637-73-6/Atrial Natriuretic Factor; EC, Atrial Natriuretic Factor; EC natriuretic factor receptor C

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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