Published Online
on September 13, 2004

A more recent version of this article appeared on September 28, 2004

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Submitted on March 30, 2004
Revised on June 1, 2004
Accepted on June 3, 2004

Sensing Tissue Ischemia. Another New Function for Capsaicin Receptors?

Hui-Lin Pan MD, PhD^* and Shao-Rui Chen MD

From the Department of Anesthesiology, Pennsylvania State University College of Medicine, and the Milton S. Hershey Medical Center, Hershey, Pa.

^* To whom correspondence should be addressed. E-mail: hpan{at}psu.edu.

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 µg/mL bradykinin in a reproducible manner. Topical application of a specific VR₁ antagonist, iodoresiniferatoxin (50 µmol/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 µmol/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.

Key words: pain • coronary disease • nervous system • angina

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