STUDIES ON THE ENDOTHELIN-1-INDUCED CONTRACTION OF RAT GRANULATION-TISSUE POUCH MEDIATED BY MYOFIBROBLASTS

A granulation tissue pouch, mostly composed of myofibroblasts, was pre pared by injecting rats subcutaneously with croton oil. The contractio n of the granulation tissue pouch caused by endothelin-1 (ET-1) and th e effects of the ET receptor antagonists, BQ123 and BQ788 on it were t hus examined. ET-1 produced contractions in a dose-dependent manner. P retreatment with BQ123, an ETA receptor selective antagonist, shifted the dose-response curve to the right, whereas pretreatment with BQ788, an ETB receptor selective antagonist, showed little effect. IRL1620, an ETB receptor selective agonist, did not cause any contraction in th e granulation tissue pouch. The existence of both ETA and ETB receptor s in the granulation tissue pouch and in cultured myofibroblasts was d emonstrated by RT-PCR. Intracellular Ca2+ mobilization in Fura-2/acety l-methoxy ester loaded cultured myofibroblasts isolated from the granu lation tissue was also examined. ET-1 produced a transient increase in [Ca2+](i) followed by a sustained elevation of [Ca2+](i), whereas IRL 1630 caused only a transient peak. These results suggest that the ET-1 induced contraction of granulation tissue is mainly mediated through the mobilization of Ca2+ from the extracellular space caused by stimul ation with ETA receptor. (C) 1998 Elsevier Science B.V. All rights res erved.