VASCULAR-RESPONSE OF TUMOR AND NORMAL-TISSUES TO ENDOTHELIN-1 FOLLOWING ANTAGONISM OF ETA AND ETB RECEPTORS IN ANESTHETIZED RATS

Modification of blood flow by endothelin-1 (ET-1) was examined in the s.c. HSN fibrosarcoma and compared to normal tissues of anaesthetised CBH/CBi rats, The ET receptor subtypes involved in the response were i nvestigated using the ETA and ETB receptor antagonists BQ-610 and BQ-7 88, respectively. Blood flow and vascular resistance were determined u sing the uptake of radiolabelled iodo-antipyrine (I-125-IAP). BQ-610 o r BQ-788 was infused for 30 min prior to blood flow determination. ET- 1 was administered 15 min into the infusion time. BQ-610 and BQ-788 in fused alone did not modify any vascular parameters, Tumour blood flow increased slightly following ET-1, contrasting with most normal tissue s, in which blood flow was reduced, Vascular resistance increased in a ll tissues, including the tumour. Neither antagonist significantly mod ified the ET-1-induced changes in tumour blood flow or vascular resist ance, whereas in the majority of normal tissues BQ-610 attenuated and BQ-788 potentiated the vascular resonse to ET-1, Our results show that the HSN tumour vasculature is only weakly responsive to ET-1 and anta gonism of its effects by BQ-610 and BQ-788, This contrasts with the ma jority of normal tissues, in which ET-1 induces an intense vasoconstri ction. (C) 1997 Wiley-Liss, Inc.