RELAXIN, A POTENT MICROCIRCULATORY EFFECTOR, IS NOT ANGIOGENIC

The ability of relaxin (RLX), which is a potent microcirculatory effec tor in many species including the rat, to induce de novo angiogenesis in vascularized mammalian tissue was tested using the rat mesenteric-w indow angiogenesis assay. RLX was administered intraperitoneally on da ys 1-5 at doses of 0.33, 3.3 and 33 nM. Controls received the vehicle by the same route. Groups of animals were sacrificed at the end of the Ist,,nd and 3rd weeks. Using computer-aided microscopic morphometry i ncluding image analysis, the response was quantified by sensitive, tec hnically independent, highly reproducible methods in terms of the vasc ularized area (VA), a measure of microvascular spatial extension, and the microvascular length (MVL), a measure of microvascular density. Th e total MVL was computed from VA x MVL. The results obtained show that RLX did not cause significant changes in any of the variables tested, regardless of dose and observation time. These findings indicate that RLX is apparently unable to mediate significant de novo angiogenesis in the system used in contrast to previously tested angiogens such as basic fibroblast growth factor, vascular endothelial growth factor, is oform 165, and tumor necrosis factor-alpha. In previous studies, RLX h as been shown to exert antitumor activity on breast cancer cells in vi tro. In the search for a possible role for RLX as an anticancer agent in vivo, it is important to know that this peptide is not angiogenic, since de novo angiogenesis is known to be a prerequisite for tumor gro wth and metastatic spread.