Up-regulation of angiotensin-converting enzyme and angiotensin II type 1 receptor in irradiated rats

Abstract

Purpose: To investigate changes in cardiac functional parameters and the cardiac expression of angiotensin-converting enzyme (ACE), angiotensin II type 1 receptor (AT1), procollagen type I (proc-I) and transforming growth factor-β1 (TGF-β1) in rats irradiated at heart.

Material and methods: Male Wistar rats were irradiated with a single dose of radiation (0, 5, 10 and 15 Gray [Gy]) delivered directly to the heart and the molecular evaluations were performed at various times post-irradiation (two days, 15 days and four months). The expression of ACE, AT1, proc-I and TGF-β1 were analysed using Real Time-Polymerase Chain Reaction (RT-PCR) and/or Western blotting. Cardiac structural and functional alterations were investigated at the four-month time point by echocardiography and by quantitative methods (stereology).

Results: Rats irradiated with 15 Gy showed a modest reduction in the ejection fraction. Cardiac proc-I, TGF-β1, ACE and AT1 were also measurably increased.

Conclusions: Irradiated rat hearts show simultaneous elevations in renin-angiotensin system components AT1 and ACE and cardiac remodeling markers proc-I and TGF-β1.

Keywords:

• TGF-β1
• fibrosis
• ACE
• AT1
• ionising radiation
• heart

Acknowledgements

We thank Tathiany Marinho, Alfonso Meléndez, Anna Coimbra, Jorge Oliveira and Alessandra Peres for technical help. The research and authors were supported by grants from CNPq, FAPERJ, UFRJ, UERJ and LCR.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.