HETEROGENEITY OF ENDOTHELIN ET(A) RECEPTOR-MEDIATED CONTRACTIONS IN THE RABBIT SAPHENOUS-VEIN

The involvement of endothelin ET(A) receptors in endothelin-1-induced contractions of the rabbit saphenous vein was studied. After desensiti zation of endothelin ET(B) receptors by pretreatment with sarafotoxin S6c, endothelin-1 and sarafotoxin S6b and a high concentration of endo thelin-3 caused dose-dependent contractions. However, endothelin-1-ind uced contractions were much less sensitive to an endothelin ET(A) rece ptor antagonist, BQ-123 (cyclo(-D-AsP-L-Pro-D-Val-L-Leu-D-Trp-)), than sarafotoxin S6b-induced responses. The pA(2) values of BQ-123 for end othelin-1- and sarafotoxin S6b-induced contractions were 5.69 and 7.65 , respectively. These results suggest pharmacological heterogeneity of endothelin ET(A) receptors in the rabbit saphenous vein.