Stimulation of angiogenesis by adenosine on the chick chorioallantoic membrane.

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Abstract
The effect of adenosine on the vascular density of the chick chorioallantoic membrane was studied. Elvax polymer pellets containing 0.2-3.0 mg of adenosine were placed on the chorioallantoic membrane of 10-day embryos. Control pellets containing mannitol were placed at least 1 cm away. After 4 days the membrane was formalin-fixed and removed. A thin plastic coverslip, inscribed with concentric circles (4-8 mm in diameter), was placed over the pellet. A vascular density index was estimated at 20 X by counting the number of intercepts between vessels and the inscribed circles. Adenosine stimulated a dose-dependent increase (p less than 0.01) in the vascular density index with the 3-mg pellets inducing a 15% increase. Inosine, a major metabolite of adenosine, did not cause a change in the number of intercepts counted. The adenosine-stimulated increase in vascularity was blocked with 110 micrograms of methyl-isobutyl-xanthine injected daily into the albumin. Partial inhibition was observed with 55 micrograms/day. Methyl-isobutyl-xanthine by itself did not affect the vascular density index. Dipyridamole enhanced adenosine's stimulation of vascular growth an additional 52%. Given alone, however, it had no effect on the membrane's vascularity. These data support an angiogenic role for adenosine. The modest, but consistent, increase in the vascular density index stimulated by adenosine, and the fact that it may be released during tissue hypoxia, is consistent with an hypothesis that this nucleoside plays a modulatory role in vessel proliferation accompanying conditions of long-term hypoxia.