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Am J Physiol Heart Circ Physiol. 2018 May 1;314(5):H954-H966. doi: 10.1152/ajpheart.00593.2017. Epub 2018 Jan 16.

Cardiac vanilloid receptor-1 afferent depletion enhances stellate ganglion neuronal activity and efferent sympathetic response to cardiac stress.

Author information

1
University of California, Los Angeles (UCLA) Cardiac Arrhythmia Center and UCLA Neurocardiology Research Center of Excellence, UCLA, Los Angeles, California.

Abstract

Afferent fibers expressing the vanilloid receptor 1 (VR1) channel have been implicated in cardiac nociception; however, their role in modulating reflex responses to cardiac stress is not well understood. We evaluated this role in Yorkshire pigs by percutaneous epicardial application of resiniferatoxin (RTX), a toxic activator of the VR1 channel, resulting in the depletion of cardiac VR1-expressing afferents. Hemodynamics, epicardial activation recovery intervals, and in vivo activity of stellate ganglion neurons (SGNs) were recorded in control and RTX-treated animals. Stressors included inferior vena cava or aortic occlusion and rapid right ventricular pacing (RVP) to induce dyssynchrony and ischemia. In the epicardium, stellate ganglia, and dorsal root ganglia, immunostaining for the VR1 channel, calcitonin gene-related peptide, and substance P was significantly diminished by RTX. RTX-treated animals exhibited higher basal systolic blood pressures and contractility than control animals. Reflex responses to epicardial bradykinin and capsaicin were mitigated by RTX. Cardiovascular reflex function, as assessed by inferior vena cava or aortic occlusion, was similar in RTX-treated versus control animals. RTX-treated animals exhibited resistance to hemodynamic collapse induced by RVP. Activation recovery interval shortening during RVP, a marker of cardiac sympathetic outflow, was greater in RTX-treated animals and exhibited significant delay in returning to baseline values after cessation of RVP. The basal firing rate of SGNs and firing rates in response to RVP were also greater in RTX-treated animals, as was the SGN network activity in response to cardiac stressors. These data suggest that elimination of cardiac nociceptive afferents reorganizes the central-peripheral nervous system interaction to enhance cardiac sympathetic outflow. NEW & NOTEWORTHY Our work demonstrates a role for cardiac vanilloid receptor-1-expressing afferents in reflex processing of cardiovascular stress. Current understanding suggests that elimination of vanilloid receptor-1 afferents would decrease reflex cardiac sympathetic outflow. We found, paradoxically, that sympathetic outflow to the heart is instead enhanced at baseline and during cardiac stress.

KEYWORDS:

cardiac afferent nerves; sympathoexcitation; transient receptor potential vanilloid 1; vanilloid receptor 1

PMID:
29351450
PMCID:
PMC6008140
DOI:
10.1152/ajpheart.00593.2017
[Indexed for MEDLINE]
Free PMC Article

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