Peachey J A, Kitchen I
Department of Biochemistry, University of Surrey, U.K.
J Cardiovasc Pharmacol. 1991;17 Suppl 7:S190-3. doi: 10.1097/00005344-199100177-00054.
Responses to endothelin-1 (ET-1) were studied in both rat and guinea pig tracheal chains in vitro. Indomethacin potentiated contractile responses to ET-1 in the guinea pig but had no effect in the rat. Furthermore, relaxation responses to ET-1 observed in some guinea pig preparations only were abolished by indomethacin. Studies using repeated full cumulative dose-response curves and repeated single-dosing techniques demonstrated tachyphylaxis to ET-1 in both rat and guinea pig. However, the degree of tachyphylaxis in the guinea pig was dependent on the initial response to the peptide, and in single-dose studies in this species, tachyphylaxis to ET-1 was more prominent in the presence of indomethacin. It is suggested that both tachyphylaxis and inconsistent release of cyclooxygenase products may be responsible for the wide differences in potency estimates for ET-1 that have been observed in airways smooth muscle.
在体外对大鼠和豚鼠气管链中内皮素 -1（ET -1）的反应进行了研究。吲哚美辛增强了豚鼠对ET -1的收缩反应，但对大鼠没有影响。此外，仅在一些豚鼠制剂中观察到的对ET -1的舒张反应被吲哚美辛消除。使用重复的全累积剂量 -反应曲线和重复单剂量技术的研究表明，大鼠和豚鼠对ET -1均出现快速耐受性。然而，豚鼠的快速耐受程度取决于对该肽的初始反应，并且在该物种的单剂量研究中，在吲哚美辛存在的情况下，对ET -1的快速耐受性更为明显。有人提出，快速耐受性和环氧化酶产物的不一致释放可能是导致在气道平滑肌中观察到的ET -1效力估计存在广泛差异的原因。
