Increased sensitivity to ET-1 in rat cerebral arteries following organ culture.
Endothelin-1 (ET-1) is recognized as being involved in the pathophysiology of cerebrovascular diseases. Using organ culture as a model for possible pathological changes we studied changes in ET(A) and ETB receptor function using a sensitive in vitro method. We observed an up-regulation of the ET(B) receptor and an amazingly increased sensitivity to ET-1 by 3 log units in pEC50; pEC50(fresh) was 8.7 +/- 0.1, and pEC50(cultured) was 11.7 +/- 0.3. pA2 for FR139317 in the fresh vessel was 7.0 +/- 0.2 whereas it could not be obtained for the cultured vessel, indicating a possible cross-talk between the ET(A) and ET(B) receptors. The increased sensitivity to ET-1 could also take place during cerebrovascular disease such as stroke or haemorrhage rendering the vessels considerably more sensitive to ET-1.
Hansen-Schwartz
J
J
Department of Clinical Experimental Research, University of Copenhagen, Glostrup Hospital, Denmark.
Edvinsson
L
L
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001488:Basilar Artery / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D001713:Biphenyl Compounds / Q000494:pharmacology; D004151:Dipeptides / Q000494:pharmacology; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology; D009924:Organ Culture Techniques; D051381:Rats; D011921:Rats, Inbred WKY; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000819:agonists / Q000378:metabolism; D014661:Vasoconstriction; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014757:Viper Venoms / Q000494:pharmacology
D001381:Azepines; D001713:Biphenyl Compounds; D004151:Dipeptides; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; C098287:IRL 2500; D007211:Indoles; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D014662:Vasoconstrictor Agents; D014757:Viper Venoms; C057354:sarafotoxins s6; C079574:FR 139317