Induction of Growth Factors in Rat Cardiac Tissue by X Irradiation

To investigate the relationship between angiogenic growth factors and endothelial enzyme activity in capillaries after injury of rat cardiomyocytes caused by X irradiation, 7-week-old male Wistar rats were anesthetized with pentobarbitone and their hearts irradiated (X rays, 20 Gy) through a hole in the lead casing in which they were enclosed. The hearts were excised at 1 h, 1 week and 3 weeks after irradiation. Left ventricular cross sections were stained for capillary enzymes by double staining for two endothelial enzymes, alkaline phosphatase (AP) and dipeptidylpeptidase IV (DPP), immunohistochemically stained for basic fibroblast growth factor (Fgf, also known as bFgf) and vascular endothelial growth factor (Vegf), and stained for nick end-labeling of DNA by the TUNEL method. Staining for distribution of AP in the arteriolar portion was reduced at both 1 and 3 weeks after irradiation with 20 Gy, but staining for DPP in the venular portion was unchanged, suggesting a close relationship between growth factors and injury of the arteriolar capillary portion. Fgf and Vegf proteins were present within the cytoplasm of the cardiomyocytes, or around capillaries, 1 h, 1 week and 3 weeks after irradiation. Many TUNEL-stained cardiomyocyte nuclei were observed at 1 h, but they had decreased markedly at 1 week and had almost disappeared by 3 weeks after irradiation. Thus Fgf and Vegf were induced concomitantly with the decrease in the staining for endothelial AP by 20 Gy X irradiation, which also caused microeffects as indicated by TUNEL staining of many nuclei at 1 h postirradiation.