Vasodilating effect and tissue accumulation of prostaglandin E-1 incorporated in lipid microspheres on the rat ductus arteriosus

Prostaglandin E-1 incorporated in lipid microspheres (lipo PGE(1)) was admi nistered to the umbilical vein of neonatal rats. Morphological measurement and quantitative autoradioluminography assessed the relationship between th e vasodilating effect and tissue accumulation of lipo PGE(1) in the ductus arteriosus. In the morphological measurement under microscopy, the inner di ameter ratio of the ductus arteriosus to the main pulmonary artery after in fusion of H-3-labeled lipo PGE(1) (H-3-lipo PGE(1)) continued to remain sig nificantly higher than that of free H-3-PGE(1). Autoradioluminography of th e frozen frontal section of neonates after intravenous infusion of H-3-lipo PGE(1) for 2 h revealed that the ductus levels of radioactivity were highe r than those of free H-3-PGE(1) in saline solution, although the blood leve ls were almost equal. Localization of lipo PGE(1) labeled with a lipophilic fluorescent probe, 1,1'-dioctadecyl-3,3,3:3'-tetramethyl-indocarbocyanine perchlorate (diI), in the endothelial cells of the ductus arteriosus was co nfirmed by confocal laser scanning microscopy. These findings suggest that the incorporation of lipid microspheres by the endothelial cells is one of the mechanisms that enables lipo PGE(1) to accumulate to higher levels in t he ductus tissue and to act more efficiently than free PGE(1) in neonatal r ats.