Vascular Response of Tumour and Normal Tissues to Endothelin-1 Following Antagonism of ET(A) and ET(B) Receptors in Anaesthetised 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 investigated using the ET(A) and ET(B) receptor antagonists BQ-610 and BQ-788, respectively. Blood flow and vascular resistance were determined using the uptake of radiolabelled iodo-antipyrine (125I-IAP). BQ-610 or 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 infused alone did not modify any vascular parameters. Tumour blood flow increased slightly following ET-1, contrasting with most normal tissues, in which blood flow was reduced. Vascular resistance increased in all tissues, including the tumour. Neither antagonist significantly modified the ET-1-induced changes in tumour blood flow or vascular resistance, 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 antagonism of its effects by BQ-610 and BQ-788. This contrasts with the majority of normal tissues, in which ET- 1 induces an intense vasoconstriction.