title: Role of the bradykinin B2 receptor in a rat model of local heart irradiation.
abstract: OBJECTIVE
  Radiation-induced heart disease (RIHD) is a delayed effect of radiotherapy for cancers of the chest, such as breast, esophageal, and lung. Kinins are small peptides with cardioprotective properties. We previously used a rat model that lacks the precursor kininogen to demonstrate that kinins are involved in RIHD. Here, we examined the role of the kinin B2 receptor (B2R) in early radiation-induced signaling in the heart.
  
  
  METHODS
  Male Brown Norway rats received the B2R-selective antagonist HOE-140 (icatibant) via osmotic minipump from 5 days before until 4 weeks after 21 Gy local heart irradiation. At 4 weeks, signaling events were measured in left ventricular homogenates and nuclear extracts using western blotting and real-time polymerase chain reaction. Numbers of CD68-positive (monocytes/macrophages), CD2-positive (T-lymphocytes), and mast cells were measured using immunohistochemistry.
  
  
  RESULTS
  Radiation-induced c-Jun phosphorylation and nuclear translocation were enhanced by HOE-140. HOE-140 did not modify endothelial nitric oxide synthase (eNOS) phosphorylation or alter numbers of CD2-positive or mast cells, but enhanced CD68-positive cell counts in irradiated hearts.
  
  
  CONCLUSIONS
  B2R signaling may regulate monocyte/macrophage infiltration and c-Jun signals in the irradiated heart. Although eNOS is a main target for kinins, the B2R may not regulate eNOS phosphorylation in response to radiation.
authors.affiliation: a Department of Pharmacology and Toxicology , University of Arkansas for Medical Sciences , Little Rock, Arkansas , USA.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Lieblong
authors.affiliation: b Division of Radiation Health, Department of Pharmaceutical Sciences , University of Arkansas for Medical Sciences , Little Rock, Arkansas , USA.
authors.forename: Vijayalakshmi
authors.initials: V
authors.lastname: Sridharan
authors.affiliation: a Department of Pharmacology and Toxicology , University of Arkansas for Medical Sciences , Little Rock, Arkansas , USA.
authors.forename: Anup K
authors.initials: AK
authors.lastname: Srivastava
authors.affiliation: c Moffitt Cancer Center and Research Institute , Department of Radiation Oncology , Tampa, Florida , USA.
authors.forename: Eduardo G
authors.initials: EG
authors.lastname: Moros
authors.affiliation: b Division of Radiation Health, Department of Pharmaceutical Sciences , University of Arkansas for Medical Sciences , Little Rock, Arkansas , USA.
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Sharma
authors.affiliation: b Division of Radiation Health, Department of Pharmaceutical Sciences , University of Arkansas for Medical Sciences , Little Rock, Arkansas , USA.
authors.forename: Marjan
authors.initials: M
authors.lastname: Boerma
mesh_terms: D000818:Animals; D006321:Heart / Q000528:radiation effects; D006331:Heart Diseases / Q000209:etiology* / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D011829:Radiation Dosage; D011832:Radiation Injuries / Q000209:etiology* / Q000378:metabolism*; D011878:Radiotherapy / Q000009:adverse effects; D051381:Rats; D043782:Receptor, Bradykinin B2 / Q000378:metabolism*
chemical_list: D043782:Receptor, Bradykinin B2
keywords: B2 receptor; Bradykinin; c-Jun; heart; macrophages