Effect of endothelin-1 and sarafotoxin S6c on blood flow in a rat tumor.
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.
Bell
K M
KM
Tumour Microcirculation Group, Gray Laboratory, Mount Vernon Hospital, Northwood, Middlesex, England.
Prise
V E
VE
Chaplin
D J
DJ
Tozer
G M
GM
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D016232:Endothelins / Q000494:pharmacology*; D005260:Female; D005354:Fibrosarcoma / Q000098:blood supply; D051381:Rats; D012039:Regional Blood Flow / Q000187:drug effects; D012513:Sarcoma, Experimental / Q000098:blood supply*; D014655:Vascular Resistance / Q000187:drug effects; D014757:Viper Venoms / Q000494:pharmacology*
D016232:Endothelins; D014757:Viper Venoms; C057354:sarafotoxins s6