Endothelin-1 (ET-1) causes vasodilatation via its
endothelin-B receptors. ET-1,
endothelin-3 and
endothelin-B receptors are known to be overexpressed in
breast carcinoma tissue. However, the functional role of ET-1 in
tumor vasculature is still unknown. If ET-1 causes an increase in
breast tumor perfusion, it could be used to increase delivery of chemotherapeutic agents to the
tumor tissues. Female Sprague-Dawley rats (180-200 g) were treated with either saline or
N-methyl, N-nitrosourea (50 mg/kg, intraperitoneally), a chemical
carcinogen. Each group was treated with: (a) ET-1 (50 ng/kg/minute, 30 minute infusion) (n = 6); or (b)
BQ788, an
endothelin-B receptor antagonist (0.33 mg/kg/minute, 20 minute infusion) + ET-1 (50 ng/kg/minute, 30 minute infusion) (n = 5). Blood flow to
tumor and normal breast tissue was measured using radioactive
microspheres. Blood perfusion to the breast and
tumor tissue was measured using
laser Doppler flowmetry. Blood flow to
tumor tissue increased (153%; P < 0.05) and vascular resistance decreased following ET-1 infusion. Blood flow to other organs was not affected.
Laser Doppler flowmetry showed an increase (176%; P < 0.05) in
breast tumor perfusion following ET-1 infusion. The increase in perfusion was attenuated (-25.2%; P < 0.05) with the administration of
BQ788. Results indicate that ET-1 induced an increase in blood flow to
tumors in
tumor-bearing rats, which is mediated by
endothelin-B receptors.