EPICARDIAL MESOTHELIAL CELLS SYNTHESIZE AND RELEASE ENDOTHELIN

Adult rat ventricular cardiocytes, when cocultured with epicardial mes othelial cells (EMC), demonstrate remarkable plasticity of phenotype a ccompanied by a significant increase in cardiocyte contractile protein content, suggesting that a factor with growth-promoting properties ma y take part in EMC-adult rat ventricular cardiocyte interactions. Endo thelin (ET) has been shown to induce cell hypertrophy, including enhan cement of expression of muscle-specific genes. We investigated the abi lity of EMC to synthesize and release ET. By light microscopy, specifi c immunostaining, with either ET-1 or Big ET-1 antibodies, was visuali zed in EMC as a fine punctate distributed throughout the cytoplasm. Re verse phase-high performance liquid chromatography (HPLC) of epicardia l mesothelial cells conditioned medium showed several peaks of immunor eactive ET. The major peak eluted with the same retention time as that of ET-1. By Northern blot analysis, a specific 2.3-kilobase (kb) mRNA species was detected by hybridization to a cDNA insert encoding for r at prepro-ET-1. ET accumulated in the culture medium in a time-depende nt manner, whereas cell content remained comparatively low. Angiotensi n II (AII) dose-dependently stimulated release of immunoreactive ET in to the culture medium.