Tumour blood flow modification by endothelin-related peptides in the rat HSN fibrosarcoma

Modification of tissue blood flow and tissue vascular resistance was examined in the female CBH rat, bearing a HSN fibrosarcoma, following bolus 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 125I-labelled-iodoantipyrine. ET-1 and SX6c produced increases in mean arterial blood pressure (MABP) of 52 mmHg and 42 mmHg respectively. Blood flow to the tumour was unaffected by ET-1 treatment, whereas blood flow to normal tissues was reduced, the exception being the heart and the brain in which flow was increased. In contrast, tumour blood flow following SX6c was significantly increased, whereas blood flow 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 vasculature was constricting via ETA receptor activation. SX6c however, did not modify tumour vascular resistance, whereas it increased vascular resistance in all normal tissues, suggesting that the tumour lacks a functional population of ETB receptors. This discrepancy may provide a means for selectively modifying tumour blood flow.