INCREASED ENDOTHELIN ETB CONTRACTILE ACTIVITY IN CULTURED SEGMENTS OFHUMAN TEMPORAL ARTERY

Contractions induced by endothelin-1, endothelin-3 and the selective E TB agonist, sarafotoxin S6c, were studied in segments of human tempora l artery. The results in fresh arteries were compared with those obtai ned alter 1 or 4 days in organ culture, and with the specific ETA anta gonist FR 139317, the specific, mixed antagonist bosentan, or the spec ific ETB antagonist, BQ 788. Sarafotoxin S6c induced no contractile ac tivity in fresh artery segments, but elicited marked contractions afte r culture. This contraction was only slightly inhibited by FR 139317, but was abolished by BQ 788. Contractions induced by endothelin-1 were antagonized by FR 139317 and bosentan, but not by BQ 788. Organ cultu re did not change the overall pattern, but all concentration-response curves were shifted leftwards. Contractions induced by endothelin-3 we re abolished by all antagonists in fresh arteries, but some activity w as restored after organ culture. Sensitivity to endothelin-3 was marke dly increased. The results suggest a change in endothelin receptors du ring organ culture, resulting in a marked increase in contractile ETB activity, and possibly some increase in ETA activity. Such changes ill ustrate the complexity of endothelin responses in this vascular bed.