Biosynthesis and modulation of endothelin from bovine pulmonary arterial endothelial cells

The biosynthesis and modulation of the vasoconstrictor peptide endothelin was studied in the conditioned medium from cultured bovine pulmonary artery endothelial (BPAE) cells. Conditioned medium from cultured BPAE cells produced contraction of isolated rabbit aortic rings. Incubation of BPAE cells with the protease inhibitors TPCK or isatoic anhydride attenuated the extent of conditioned medium-induced contractions. Incubation of BPAE cells with thrombin produced an enhancement of conditioned medium-induced contraction by approximately 25%. Endothelin levels in conditioned medium were measured by RIA and incubation of BPAE cells with TPCK or isatoic anhydride significantly reduced endothelin levels, whereas incubation with thrombin or transforming growth factor beta-1 stimulated the levels of endothelin in the conditioned medium. These data indicate that endothelin may be modulated by certain protease inhibitors and by platelet and immune cell mediators and suggest a potential new mode of vascular tone regulation.