Faculty Collaboration Database

Hypoxia stimulates prostacyclin synthesis in newborn pulmonary artery endothelium by increasing cyclooxygenase-1 protein. Circ Res 1994 Jul;75(1):33-40

Date

07/01/1994

Pubmed ID

8013080

DOI

10.1161/01.res.75.1.33

Scopus ID

2-s2.0-0028360866 (requires institutional sign-in at Scopus site)   46 Citations

Abstract

In newborn lambs, pulmonary prostacyclin (PGI2) production increases acutely in response to low oxygen. We tested the hypothesis that decreased oxygenation directly stimulates PGI2 synthesis in arterial segments and cultured endothelial cells from newborn lamb intrapulmonary arteries. In segments studied at PO2 of 680 mm Hg, the synthesis of PGI2 exceeded prostaglandin E2 (PGE2) by 73%. Endothelium removal lowered PGI2 by 77% and PGE2 by 66%. At low oxygen tension (PO2, 40 mm Hg), PGI2 and PGE2 synthesis rose by 96% and 102%, respectively. Similarly, in endothelial cells studied at PO2 of 680 mm Hg, the synthesis of PGI2 exceeded PGE2 by 50%, and at low oxygen tension both PGI2 and PGE2 increased (89% and 64%, respectively). Endothelial cell PGI2 synthesis maximally stimulated by bradykinin, A23187, or arachidonic acid was also increased at low PO2 by 50%, 66%, and 48%, respectively. PGE2 synthesis was similarly altered, increasing by 33%, 37%, and 41%, respectively. In contrast, lowering oxygen had minimal effect on PGI2 and PGE2 synthesis with exogenous PGH2, which is the product of cyclooxygenase. Immunoblot analyses revealed that there was a 2.6-fold greater abundance of cyclooxygenase-1 protein at PO2 of 40 versus 680 mm Hg, and the increase at lower oxygen tension was inhibited by cycloheximide. The cyclooxygenase-2 isoform was not detected. Thus, attenuated oxygenation directly stimulates PGI2 and PGE2 synthesis in intrapulmonary arterial segments and endothelial cells from newborn lambs. This process is due to enhanced cyclooxygenase activity related to increased abundance of the cyclooxygenase-1 protein, and this effect may be due to increased synthesis of the enzyme protein.

Author List

North AJ, Brannon TS, Wells LB, Campbell WB, Shaul PW

Author

William B. Campbell PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Animals, Newborn
Cells, Cultured
DNA-Binding Proteins
Endothelium, Vascular
Epoprostenol
Hypoxia
Oxygen
Prostaglandin-Endoperoxide Synthases
Prostaglandins
Pulmonary Artery
Sheep
Stimulation, Chemical
Viral Proteins