s6c-sarafotoxin and 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.

Topics: Animals; Blood Pressure; Endothelin-1; Female; Fibrosarcoma; Rats; Regional Blood Flow; Vascular Resistance; Viper Venoms

The modification of tumor blood flow resulting from administration of endothelin-1 (ET-1) and sarafotoxin S6c (SX6c) was examined in female CBH rats. Blood flow in subcutaneous HSN tumors and normal tissues was measured by tissue uptake of 125I-labeled iodoantipyrine ([125I])IAP). A 75% increase in tumor blood flow was observed after 1 nM/kg ET-1, contrasting with flow in normal tissue, which was unaffected or reduced. The exception to this was the brain, in which blood flow was increased by 30%, resulting from a rise in mean arterial blood pressure (MABP) and the absence of vasoconstriction. Paradoxically, a significant drop in the tumor vascular resistance was observed after 1 nM/kg ET-1, whereas in all other tissues the vascular resistance was significantly increased. Vascular responses to SX6c differed from those observed with ET-1. At 1 nM/kg SX6c, blood flow in the tumor was increased to 175% of the control as a result of the increase in MABP, which was similar to ET-1. However, unlike ET-1, there was no associated vasodilatation. Vascular resistance was increased in all normal tissues with 1 nM/kg SX6c, corresponding to decreases in blood flow in the contralateral skin, skeletal muscle, and small intestine. This study therefore demonstrates that the vascular responses to ET-1 and SX6c are unique in the HSN tumor compared to normal tissues. This atypical response of the tumor vasculature may therefore be exploitable to improve the delivery of blood-borne anti-cancer agents in therapy.

Topics: Animals; Blood Pressure; Endothelins; Female; Fibrosarcoma; Rats; Regional Blood Flow; Sarcoma, Experimental; Vascular Resistance; Viper Venoms

Topics: Animals; Clone Cells; Endothelins; Fibrosarcoma; Inositol Phosphates; Mice; Receptors, Cell Surface; Receptors, Cholinergic; Receptors, Endothelin; Receptors, Peptide; Tumor Cells, Cultured; Viper Venoms