Endothelin Stimulates Cardiac Sympathetic Afferents during Myocardial Ischemia

Abstract

Myocardial ischemia activates cardiac sympathetic afferents that transmit nociceptive information to the brain leading to chest pain and excitatory cardiovascular reflexes. Previous studies have demonstrated an increase in endothelin (ET) concentrations during myocardial ischemia and unstable angina. ET-1 can elicit pain in animal models through stimulation of somatic sensory nerve fibers. Therefore, the present study tested the hypothesis that ET stimulates ischemically sensitive cardiac afferents and thus contributes to activation of this pathway during ischemia. Nerve activity of single unit cardiac afferents was recorded from the left sympathetic chain or rami communicans (T2 - T5) in anesthetized cats. Receptive fields of 11 afferents (CV= 0.31–3.25 m/s) were identified in the left ventricle with a stimulating electrode. Five min of myocardial ischemia stimulated all 11 cardiac afferents (2 Aδ, 9 C-fibers), increasing their activity from 0.52±0.23 to 2.34±0.45 imp/s. Injection of ET-1 (2–4 μg) into the left atrium (LA) stimulated five ischemically sensitive cardiac afferents, after a latency of 17±2.6 s, significantly increasing the activity of these afferents from 0.31±0.04 to 1.41±0.34 imp/s. BQ123, a selective ETA receptor antagonist, eliminated the responses of three cardiac afferents to ET-1 (4 μg, LA), and attenuated the ischemia-related increase in activity of three other afferents by 38%. These data suggest that during ischemia endothelin contributes to stimulation of cardiac sympathetic afferent nerve endings through an ETA receptor mechanism. (Supported by NIH HL66217)