Effects of cobalt-60 gamma-radiation on the synthesis of adrenomedullin and endothelin in rat vascular smooth muscle cells.

Abstract

We studied the effects of cobalt-60 Gamma-radiation on the gene expression and secretion of adrenomedullin (Adm) and endothelin (ET) in cultured rat vascular smooth muscle cells (VSMCs). Rat VSMCs cultured in Dulbecoo's modified Eagle's medium containing 10% FBS were radiated with cobalt-60 Gamma-radiation at doses of 1, 14, and 25 Gy, respectively. Then the mRNA of Adm and ET in VSMCs were detected by the reverse-transcriptative competitive polymerase chain reaction. Adm and ET levels in rat VSMCs were measured by radioimmunoassay. As compared with that of the control, the secretions of Adm in rat VSMCs radiated at doses of 14 and 25 Gy were increased by 270% (P < 0.05) and 233% (P < 0.05), respectively. The mRNA levels of Adm were increased by 82.4% (P < 0.01) and 101% (P <0.01), respectively. Meanwhile, the secretions of ET were decreased by 27.3% (P < 0.01) and 58.0% (P < 0.01) in VSMCs radiated at doses of 14 and 25 Gy, respectively. In parallel, the mRNA levels of ET were decreased by 47.1% (P < 0.01) and 40.2% (P < 0.01), respectively. Radiation at a dose of 1 Gy had no significant effect on Adm and ET at the gene and protein levels. As compared with the control, the Adm/ET ratios in VSMCs increased by 65% (P > 0.05), 409% (P < 0.01), and 693% (P < 0.01), respectively, with radiation at doses of 1,14 and 25 Gy, respectively. The balance of Adm/ET in VSMCs could be changed by cobalt-60 Gamma-radiation, which might play an important role in the use of radiotherapy for restenosis.