AN ENDOTHELIAL-CELL MODEL FOR THE INVESTIGATION OF THE MOLECULAR REGULATION OF FETAL VASCULAR TONE

Human umbilical vessels are not innervated, and hence regulation of tone in these vessels must come from locally derived vasoactive substances such as prostacyclin. To evaluate the regulation of prostacyclin production by human umbilical vein endothelial cells, we incubated confluent cultures of these cells with various concentrations of inflammatory mediators (endotoxin, interleukin-1-beta, and tumor necrosis factor), protein kinase C agonists (phorbol 12-myristate 13-acetate, phorbol 12,13-dibutyrate), and calcium ionophores (A-23187 and ionomycin). Human umbilical vein endothelial cells were prepared from term pregnancies, and confluent cultures were incubated with test substances for 16 hours. Prostacyclin was measured as its metabolite 6-keto-prostaglandin F1-alpha by radioimmunoassay. Concentration-related increases in 6-keto-prostaglandin F1-alpha production were observed in response to endotoxin, cytokines, phorbol esters, and calcium ionophores. We conclude that human umbilical vein endothelial cell prostacyclin production is influenced by several intracellular messengers and that human umbilical vein endothelial cells may provide a useful in vitro model for investigating the physiology and pathophysiology of umbilical vessel vascular tone.