Effect of endothelin-1 and sarafotoxin S6c on blood flow in a rat tumor.

Abstract

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.

• Authors: K M Bell, V E Prise, D J Chaplin, G M Tozer
• Journal: Journal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 26 Suppl 3 Pg. S222-5 ( 1995) ISSN: 0160-2446 [Print] United States
• PMID: 8587370 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Endothelins
• Viper Venoms
• sarafotoxins s6

Topics

• Animals
• Blood Pressure (drug effects)
• Endothelins (pharmacology)
• Female
• Fibrosarcoma (blood supply)
• Rats
• Regional Blood Flow (drug effects)
• Sarcoma, Experimental (blood supply)
• Vascular Resistance (drug effects)
• Viper Venoms (pharmacology)