title: Roles of sensory nerves in the regulation of radiation-induced structural and functional changes in the heart.
abstract: OBJECTIVE
  Radiation-induced heart disease (RIHD) is a chronic severe side effect of radiation therapy of intrathoracic and chest wall tumors. The heart contains a dense network of sensory neurons that not only are involved in monitoring of cardiac events such as ischemia and reperfusion but also play a role in cardiac tissue homeostasis, preconditioning, and repair. The purpose of this study was to examine the role of sensory nerves in RIHD.
  
  
  METHODS
  Male Sprague-Dawley rats were administered capsaicin to permanently ablate sensory nerves, 2 weeks before local image-guided heart x-ray irradiation with a single dose of 21 Gy. During the 6 months of follow-up, heart function was assessed with high-resolution echocardiography. At 6 months after irradiation, cardiac structural and molecular changes were examined with histology, immunohistochemistry, and Western blot analysis.
  
  
  RESULTS
  Capsaicin pretreatment blunted the effects of radiation on myocardial fibrosis and mast cell infiltration and activity. By contrast, capsaicin pretreatment caused a small but significant reduction in cardiac output 6 months after irradiation. Capsaicin did not alter the effects of radiation on cardiac macrophage number or indicators of autophagy and apoptosis.
  
  
  CONCLUSIONS
  These results suggest that sensory nerves, although they play a predominantly protective role in radiation-induced cardiac function changes, may eventually enhance radiation-induced myocardial fibrosis and mast cell activity.
authors: Department of Pharmaceutical Sciences, Division of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
authors: Vijayalakshmi
authors: V
authors: Sridharan
authors: Department of Pharmaceutical Sciences, Division of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
authors: Preeti
authors: P
authors: Tripathi
authors: Department of Radiation Oncology, Division of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
authors: Sunil
authors: S
authors: Sharma
authors: Department of Radiation Oncology, Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors: Eduardo G
authors: EG
authors: Moros
authors: Department of Pharmaceutical Sciences, Division of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
authors: Junying
authors: J
authors: Zheng
authors: Department of Pharmaceutical Sciences, Division of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, Arkansas; Surgical Service, Central Arkansas Veterans Healthcare System, Little Rock, Arkansas.
authors: Martin
authors: M
authors: Hauer-Jensen
authors: Department of Pharmaceutical Sciences, Division of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, Arkansas. Electronic address: mboerma@uams.edu.
authors: Marjan
authors: M
authors: Boerma
mesh_terms: D000818:Animals; D002211:Capsaicin / Q000494:pharmacology*; D002302:Cardiac Output / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D003714:Denervation / Q000379:methods; D004452:Echocardiography / Q000379:methods; D005355:Fibrosis; D006321:Heart / Q000294:innervation* / Q000503:physiopathology / Q000528:radiation effects; D008264:Macrophages / Q000187:drug effects / Q000528:radiation effects; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009206:Myocardium / Q000473:pathology; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1 / Q000378:metabolism / Q000528:radiation effects; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2 / Q000378:metabolism / Q000528:radiation effects; D009929:Organ Size / Q000528:radiation effects; D011833:Radiation Injuries, Experimental / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects
chemical_list: C539818:Nr4a1 protein, mouse; C539883:Nr4a2 protein, mouse; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D002211:Capsaicin