Distribution of prostacyclin synthase, 6-keto-prostaglandin F1 alpha, and 15-hydroxy-prostaglandin dehydrogenase in the normal and persistent ductus arteriosus of the dog.

The presence of prostacyclin synthase (PGI2 synthase), 6-keto-prostaglandin F1 alpha (6k-PGF1 alpha), and the stable hydrolysis product of prostacyclin (PGI2), prostaglandin E2 (PGE2), as well as the activity of 15-hydroxy-prostaglandin dehydrogenase (PGDH) were studied in the aorta, pulmonary artery, the normal ductus arteriosus (DA), and persistent DA (PDA) of the dog using histochemical and immunohistochemical techniques. The normal DA is characterized by the development of intimal thickening, a process that does not occur in the persistent DA. Distribution of PGI2 synthase was identical in the aorta, pulmonary artery, and persistent DA. In these vessels endothelial cells contained higher levels of PGI2 synthase as compared with medial smooth muscle cells. In the normal DA, levels of PGI2 synthase were clearly higher in smooth muscle cells at the sites of intimal thickening than at other sites. Distribution of 6-keto-PGF1 alpha resembled the localization of PGI2 synthase. Presence of PGE2 and activity of PGDH could not be demonstrated. The results demonstrated existence of a clear relationship between ductal morphology and the presence of PGI2 synthase. This finding suggests a more important role for PGI2 in regulating ductal patency than has heretofore been appreciated. It was assumed that the role of PGI2 in regulating ductal patency is, at birth, at least overruled by the constrictive effect of the cytochrome P450 mono-oxygenase mechanism. It is still possible to attribute a role to PGI2 in the regulation of cushion formation. Once smooth muscle cell activity has been enhanced by the presence of a glycosaminoglycan rich environment, increase in PGI2 may produce a concurrent inhibition of smooth muscle cell growth.