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Int J Radiat Biol. 2015 Aug;91(8):634-42. doi: 10.3109/09553002.2015.1047041. Epub 2015 Jun 19.

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

Author information

1
a Department of Pharmacology and Toxicology , University of Arkansas for Medical Sciences , Little Rock, Arkansas , USA.
2
b Division of Radiation Health, Department of Pharmaceutical Sciences , University of Arkansas for Medical Sciences , Little Rock, Arkansas , USA.
3
c Moffitt Cancer Center and Research Institute , Department of Radiation Oncology , Tampa, Florida , USA.

Abstract

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.

KEYWORDS:

B2 receptor; Bradykinin; c-Jun; heart; macrophages

PMID:
25955317
PMCID:
PMC4743985
DOI:
10.3109/09553002.2015.1047041
[Indexed for MEDLINE]
Free PMC Article

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