TRANSCRIPTIONAL REGULATED PLASTICITY OF VASCULAR CONTRACTILE ENDOTHELIN ETB RECEPTORS AFTER ORGAN-CULTURE

The aim of the present study was to investigate the level of regulatio n of the contractile endothelin ETB receptor which appears spontaneous ly after organ culture of vascular segments. Endothelin-1 elicited a s trong contraction while the selective endothelin ETB receptor agonist, sarafotoxin 6c, had a negligible effect on fresh ring segments of rat mesenteric artery. After organ culture in serum-free Dulbecco's modif ied Eagle's medium at 37 degrees C (for 1 or 2 days) the endothelin-1- induced contraction was unchanged, whereas sarafotoxin 6c induced, aft er 1 day, a marked contraction which was further increased at day 2. T he contraction induced by sarafotoxin 6c was significantly attenuated by the transcriptional inhibitor, actinomycin D, or the translational inhibitor, cyclohexamide, while the endothelin-1-induced contraction w as much less affected. mRNA for endothelin ETA and endothelin ETB fres h human omental arteries denuded of endothelium. However, after organ culture, endothelin ETB mRNA was more prominent than endothelin ETA mR NA. Furthermore, the mRNA for both receptors was decreased after treat ment with actinomycin D but not with cyclohexamide. This suggests that the endothelin ETA receptor is the dominating contractile receptor in fresh arteries while organ culture induces transcription and subseque nt translation of contractile endothelin ETB receptors. (C) 1997 Elsev ier Science B.V.