Opposing actions of angiotensins on angiogenesis

Abstract

Using the murine sponge model of angiogenesis, associated to functional and morphological parameters we have demonstrated opposing actions of angiotensin II (Ang II) and angiotensin-(1-7;Ang-1-7) in modulating fibrovascular tissue growth. Angiogenesis in the implants was assessed at day 7 postimplantation by extracting the hemoglobin content, by determining the outflow rate of sodium fluorescein applied intraimplant and by histological analysis. Furthermore, the proliferative activity of control and angiotensin-treated implants was established using the MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2(4 -sulfonyl)2H-tetrazolium)assay. The hemoglobin content in the control implants was 2.4 +/- 0.14 (microg/mg wet weight) versus 3.6 +/- 0.27(Ang II;100 ng) and 0.86 +/- 0.07 Ang-(1-7); 20 ng. Blood flow in the implants as determined by t1/2 values (time taken for the fluorescence to reach 50% of the peak in the systemic circulation) showed that Ang II stimulated angiogenesis, whereas Ang-(1-7) inhibited it. The proliferative activity of the sponge-induced fibrovascular tissue was enhanced by Ang II and diminished by Ang-(1-7). These results show the pro-versus anti-angiogenic effects of these angiotensin molecules, providing evidence for their opposing effects on vascular tissue growth and wound healing in vivo.