TUMOR BLOOD-FLOW MODIFICATION BY ENDOTHELIN-RELATED PEPTIDES IN THE RAT HSN FIBROSARCOMA

Modification of tissue blood flow and tissue vascular resistance was e xamined in the female CBH rat, bearing a HSN fibrosarcoma, following b olus intravenous administration of 1 nM kg(-1) endothelin-1 (ET-1) or 1 nM kg(-1) sarafotoxin S6c (SX6c), selective agonists for endothelin A (ETA) and B (ETB) receptors respectively. Blood flow was measured 15 min after drug administration by the tissue uptake of I-125-labelled- iodoantipyrine. ET-1 and SX6c produced increases in mean arterial bloo d pressure (MABP) of 52 mmHg and 42 mmHg respectively. Blood flow to t he tumour was unaffected by ET-1 treatment, whereas blood flow to norm al tissues was reduced, the exception being the heart and the brain in which how was increased. In contrast, tumour blood flow following SX6 c was significantly increased, whereas blood dow in normal tissues was either unaltered or reduced. Vascular resistance was increased in all tissues and the tumour by ET-1 demonstrating that the tumour vasculat ure was constricting via ETA receptor activation. SX6c however, did no t modify tumour vascular resistance, whereas it increased vascular res istance in all normal tissues, suggesting that the tumour lacks a func tional population of ETB receptors. This discrepancy may provide a mea ns for selectively modifying tumour blood flow.