Role of the bradykinin B2 receptor in a rat model of local heart irradiation

Purpose: 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...

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Bibliographic Details
Published in:International journal of radiation biology 2015-08, Vol.91 (8), p.634-642
Main Authors: Lieblong, Benjamin J., Sridharan, Vijayalakshmi, Srivastava, Anup K., Moros, Eduardo G., Sharma, Sunil K., Boerma, Marjan
Format: Article
Language:English
Subjects:
Animals
B2 receptor
Bradykinin
c-Jun
heart
Heart - radiation effects
Heart Diseases - etiology
Heart Diseases - metabolism
macrophages
Male
Myocardium - metabolism
Radiation Dosage
Radiation Injuries - etiology
Radiation Injuries - metabolism
Radiotherapy - adverse effects
Rats
Receptor, Bradykinin B2 - metabolism
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Summary:Purpose: 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. Materials and 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.
ISSN:0955-3002
1362-3095
DOI:10.3109/09553002.2015.1047041