Low-affinity nerve growth factor receptor p75NTR immunoreactivity in the myocardium with sympathetic hyperinnervation.
BACKGROUND
We previously demonstrated the relationship between sympathetic nerve density in myocardium and the occurrences of ventricular arrhythmia. Nerve growth factor (NGF) regulates myocardial sympathetic innervation. However, it is unclear whether the NGF high-affinity receptor tyrosine kinase A (TrkA) and the NGF low-affinity receptor p75NTR are altered in the state of sympathetic hyperinnervation in the heart. The aim of this study was to determine the density and location of TrkA and p75NTR in canine ventricles with sympathetic hyperinnervation.


RESULTS
Myocardial sympathetic hyperinnervation was induced by local infusion of NGF into myocardium or left stellate ganglia, or chronic subthreshold electric stimulation to the left stellate ganglia. The results showed that TrkA immunoreactivity was absent in the myocardium. Low-affinity receptor p75NTR immunoreactivity was present in axons, Schwann cells, and interstitial cells of sympathetic nerves, as well as in interstitial cells of the myocardium. The density of p75NTR immunolabeled myocardial interstitial cells at the NGF infusion site was lower than that at the site remote from NGF infusion, yet the sympathetic nerve density was higher at the infusion site than the remote area. The density of p75NTR also was lower in the myocardium with high sympathetic nerve density, induced by NGF infusion or chronic electric stimulation of the left stellate ganglia, compared to control groups.


CONCLUSIONS
The data indicate that p75NTR may be the main NGF receptor in the myocardium, and p75NTR immunopositive interstitial cells may have a role in regulating sympathetic nerve growth in canine heart.
Zhou
Shengmei
S
Division of Cardiology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Cao
Ji-Min
JM
Swissa
Moshe
M
Gonzalez-Gomez
Ignacio
I
Chang
Che-Ming
CM
Chien
Kai
K
Miyauchi
Yasushi
Y
Fu
Katherine J
KJ
Yi
Johnny
J
Asotra
Kamlesh
K
Karagueuzian
Hrayr S
HS
Fishbein
Michael C
MC
Chen
Peng-Sheng
PS
Chen
Lan S
LS
D000818:Animals; D035061:Control Groups; D016757:Death, Sudden, Cardiac / Q000209:etiology; D004285:Dogs; D006321:Heart / Q000187:drug effects / Q000294:innervation*; D007150:Immunohistochemistry; D007260:Infusion Pumps; D009206:Myocardium / Q000276:immunology*; D020932:Nerve Growth Factor / Q000008:administration & dosage* / Q000493:pharmacokinetics; D020800:Receptor, Nerve Growth Factor / Q000276:immunology*; D020917:Receptor, trkA / Q000276:immunology*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000276:immunology*
D020800:Receptor, Nerve Growth Factor; D020932:Nerve Growth Factor; D020917:Receptor, trkA