| Author/Editor | Čemažar, M; Wilson, I; Prise, VE; Bell, KM; Hill, SA; Tozer, GM | |
| Title | The endothelin B (ETB) receptor agonist IRL 1620 is highly vasoconstrictive in two syngeneic rat tumour lines: potential for selective tumour blood flow modification | |
| Type | članek | |
| Source | Br J Cancer | |
| Vol. and No. | Letnik 93, št. 1 | |
| Publication year | 2005 | |
| Volume | str. 98-106 | |
| Language | eng | |
| Abstract | The vascular effects of the endothelin B (ETB) receptor agonist IRL I 620 were invesigated in the rat P22 carcinosarcoma and a range of normal tissues in BDIX rats. Tissue blood flow rate was calculated from measurements of tissue uptake of radiolabelled iodoantipyrine. A comparison of vascular effects in the P22 tumour and the HSN sarcoma growing in CBH/CBi rats was made using laser Doppler flowmetry, showing similar effects of IRL I 620, with red cell flux rapidly decreasing by 50-60% and then returning to control levels within approximately 30 min. This corresponded to similar levels but different spatial organisation of ETB binding sites in the two tumours, as measured by autoradiography. The decrease in tumour blood flow and an increase in vascular resistance suggest that the vascular component of ETB receptors in the P22 tumour is localised on contractile elements rather than on endothelial cells. ETA receptors were also identifed. Vasoconstriction occurred uniformly throughout the P22 tumour mass. consistent with a measured homogeneous distribution of ETB receptors. IRL I 620 caused vasoconstriction in normal skeletal muscle, kidney and small intestine of the BDIX rat as well as in tumour, but did not affect blood flow in other tissues. These effects could be useful for limiting toxicity of certain chemotherapeutic agents. Fully functional ETB receptors are clearly expressed on tumour vasculature and IRL I 620 shows promise for short-term modifcation of tumour blood flow. Expression levels of ETB receptors on the tomour vasculature could be useful for predicting which tumours are likely to respond to IRL I 620. | |
| Descriptors | CARCINOSARCOMA ENDOTHELINS PEPTIDE FRAGMENTS RECEPTORS, ENDOTHELIN VASOCONSTRICTOR AGENTS RATS BLOOD PRESSURE HEART RATE VASCULAR RESISTANCE |