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Increased endothelin ETB contractile activity in cultured segments of human temporal artery

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Contractions induced by endothelin-1, endothelin-3 and the selective ETB agonist, sarafotoxin S6c, were studied in segments of human temporal artery. The results in fresh arteries were compared with those obtained after 1 or 4 days in organ culture, and with the specific ETA antagonist FR 139317, the specific, mixed antagonist bosentan, or the specific ETB antagonist, BQ 788. Sarafotoxin S6c induced no contractile activity in fresh artery segments, but elicited marked contractions after 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 culture did not change the overall pattern, but all concentration–response curves were shifted leftwards. Contractions induced by endothelin-3 were abolished by all antagonists in fresh arteries, but some activity was restored after organ culture. Sensitivity to endothelin-3 was markedly increased. The results suggest a change in endothelin receptors during organ culture, resulting in a marked increase in contractile ETB activity, and possibly some increase in ETA activity. Such changes illustrate the complexity of endothelin responses in this vascular bed.
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Keywords: BQ 788; Bosentan; ET-A; ET-B; FR 139317; human temporal artery; organ culture; sarafotoxin S6c

Document Type: Original Article

Affiliations: 1: Department of Neurology, University Hospital of Trondheim, Norway 2: Department of Neurosurgery, University Hospital of Trondheim, Norway 3: Division of Experimental Research, Department of Internal Medicine, Lund University Hospital, Lund, Sweden

Publication date: 1998-09-01

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