Document Detail

Sensing tissue ischemia: another new function for capsaicin receptors?
MedLine Citation:
PMID:  15364816     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Chest pain is a hallmark of myocardial ischemia, but its underlying signaling mechanisms remain poorly understood. The capsaicin receptor, vanilloid receptor-1 (VR1), is an important cation channel present on primary nociceptive neurons. We have shown that the VR1 is expressed on sensory nerve endings of the heart. In the present study, we determined the role of VR1s in activation of cardiac spinal afferent nerves caused by myocardial ischemia. METHODS AND RESULTS: Single-unit activity of cardiac afferents was recorded from the sympathetic chain of anesthetized ferrets. Cardiac afferents responded to 5 minutes of regional myocardial ischemia and topical application of 10 microg/mL bradykinin in a reproducible manner. Topical application of a specific VR1 antagonist, iodoresiniferatoxin (50 micromol/L), to the receptive field of afferents produced a large attenuation of the firing activity of cardiac afferents caused by myocardial ischemia. Iodoresiniferatoxin also significantly reduced the afferent response to bradykinin applied to the receptive field. Furthermore, treatment with a VR1 channel blocker, ruthenium red (200 micromol/L), had a similar inhibitory effect on the afferent responses to myocardial ischemia and bradykinin. CONCLUSIONS: This study provides the first functional evidence that ischemic stimulation of cardiac spinal afferent nerves is mediated through VR1s. The VR1 on the cardiac sensory nerve may function as a molecular sensor to detect tissue ischemia and activate cardiac nociceptors.
Hui-Lin Pan; Shao-Rui Chen
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.     Date:  2004-09-13
Journal Detail:
Title:  Circulation     Volume:  110     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2004 Sep 
Date Detail:
Created Date:  2004-09-28     Completed Date:  2005-05-24     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1826-31     Citation Subset:  AIM; IM    
Department of Anesthesiology, H187, Pennsylvania State University College of Medicine, and the Milton S. Hershey Medical Center, 500 University Dr, Hershey, PA 17033-0850, USA.
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MeSH Terms
Action Potentials / drug effects
Afferent Pathways / drug effects,  physiopathology
Angina Pectoris / etiology,  physiopathology*
Bradykinin / pharmacology
Diterpenes / pharmacology
Heart / innervation*
Myocardial Ischemia / complications,  physiopathology*
Nerve Fibers, Unmyelinated / drug effects,  physiology*
Nociceptors / drug effects,  physiology*
Pericardium / drug effects,  innervation*
Posterior Horn Cells / drug effects,  physiology*
Receptors, Drug / antagonists & inhibitors,  physiology*
Ruthenium Red / pharmacology
Spinal Nerves / physiopathology*
Grant Support
Reg. No./Substance:
0/Diterpenes; 0/Receptors, Drug; 0/iodoresiniferatoxin; 11103-72-3/Ruthenium Red; 58-82-2/Bradykinin

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

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