REGIONAL VARIATION IN APPEARANCE OF VASCULAR CONTRACTILE ENDOTHELIN-BRECEPTORS FOLLOWING ORGAN-CULTURE

Objective: The aim of this study was to investigate the appearance of contractile endothelin (ET)-B receptors following organ culture in dif ferent vascular regions. Method: The contractile responses of vascular smooth muscle induced by ET-I and the selective ETB receptor agonist sarafotoxin 6c (S6c) were investigated in circular segments representi ng eight vascular regions in the rat (aorta, femoral artery, mesenteri c artery, branch of the mesenteric artery, proximal and distal parts o f the caudal artery, femoral and mesenteric,veins), To allow the ETB r eceptor to be expressed, the segments were placed in organ culture for 1 to 5 days. Pharmacological characterisation of the ET receptors was performed in mesenteric arterial segments. All contractile responses were measured in percentage of K+-induced contraction. Results: ET-1 i nduced strong concentration-dependent contractions of all fresh (not c ultured) segments. S6c had negligible effects on all fresh vessels wit h the exception of the mesenteric vein, where a small contraction was seen. After 1 day of organ culture all tested segments, with the excep tion of aorta and the proximal part of the caudal artery, showed conce ntration-dependent contractile responses to S6c which were further aug mented after 5 days of culture. The ET-l-induced responses were only s lightly affected by organ culture. Contractions induced by S6c were mo re enhanced in small arteries and veins than in larger arteries. Furth ermore, the S6c-induced response was more pronounced in the mesenteric region as compared to the hindlimb. In fresh mesenteric arterial segm ents FR139317 (ETA receptor antagonist) and bosentan (ETA/ETB receptor antagonist) but not IRL 2500 (ETB receptor antagonist) shifted the ET -l-induced concentration-response curve in parallel to the right. In c ontrast, after organ culture the S6c-induced concentration-response cu rves were shifted parallel to the right in the following potency order : IRL 2500 > bosentan > FR139317. Conclusion: During normal conditions , the ETA receptor is the dominating mediator of endothelin-induced co ntraction in eight different vascular regions. Furthermore, this study indicates that most of the vessels have the ability to develop contra ctile ETB receptors and that this plasticity differs in vascular regio ns. (C) 1998 Elsevier Science B.V.