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-ß1 (TGF-ß1) 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-ß1 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-ß1, 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-ß1.