Sensing tissue ischemia: another new function for capsaicin receptors?
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.


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.
Pan
Hui-Lin
HL
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. hpan@psu.edu
Chen
Shao-Rui
SR
D000200:Action Potentials / Q000187:drug effects; D000344:Afferent Pathways / Q000187:drug effects / Q000503:physiopathology; D000787:Angina Pectoris / Q000209:etiology / Q000503:physiopathology*; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D004224:Diterpenes / Q000494:pharmacology; D005289:Ferrets; D006321:Heart / Q000294:innervation*; D008297:Male; D017202:Myocardial Ischemia / Q000150:complications / Q000503:physiopathology*; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects / Q000502:physiology*; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology*; D010496:Pericardium / Q000187:drug effects / Q000294:innervation*; D020671:Posterior Horn Cells / Q000187:drug effects / Q000502:physiology*; D011955:Receptors, Drug / Q000037:antagonists & inhibitors / Q000502:physiology*; D012430:Ruthenium Red / Q000494:pharmacology; D013127:Spinal Nerves / Q000503:physiopathology*
D004224:Diterpenes; D011955:Receptors, Drug; C468130:iodoresiniferatoxin; D012430:Ruthenium Red; D001920:Bradykinin