Vascular response of tumour and normal tissues to endothelin-1 following antagonism of ETA and ETB receptors in anaesthetised rats

✍ Scribed by Katrina M. Bell; Vivien E. Prise; David J. Chaplin; Sheila Wordsworth; Gillian M. Tozer

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: French
• Weight: 155 KB
• Volume: 73
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/(sici)1097-0215(19971009)73:2<283::aid-ijc20>3.0.co;2-f

✦ Synopsis

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 ETA and ETB receptor antagonists BQ-610 and BQ-788, respectively. Blood flow and vascular resistance were determined using the uptake of radiolabelled iodo-antipyrine ( 125 I-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.