Angiogenesis is a prerequisite for the development of various vascular diseases and for the growth and metastasis of solid tumors. In this study, the effects of histamine on angiogenesis were examined using an in vitro coculture system of rat
epididymal
fat myofibroblasts and microvascular fragments.
Histamine induced prominent capillary network formation without affecting the proliferation of myofibroblasts. To determine the mechanism of histamine action on angiogenesis the changes in cell numbers, DNA synthesis, phosphorylation of ribosomal
protein S6, and cAMP content were assessed before and after the treatments of histamine-receptor antagonists. The ability of histamine to stimulate capillary network formation was blocked by pyrilamine, a H1-receptor antagonist, reflecting
histamine
acts through the H1 receptors in the capillary endothelium.
Cimetidine, a H2-receptor antagonist, itself demonstrated five fold increase of myofibroblasts proliferation along with moderate enhancement of capillary network formation. Our results suggest that cimetidine works through the reduction of cAMP
content
in myofibroblasts, thereby releasing the inhibitory effect of cAMP on myofibroblasts. Thus, myofibroblasts proliferation induced by cimetidine stimulates the production of angiogenis factors from myofibroblasts leading to indirect enhancement of
capillary network formation.
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