Biphasic stimulation of prostacyclin by endogenous nitric oxide (NO) in endothelial cells transfected with inducible NO synthase.
Nitric oxide (NO) regulates prostaglandin H synthase (PGHS) activity in various cell types, but reports conflict in regard to its stimulatory versus inhibitory role. Murine lung endothelial cells infected with a retroviral vector expressing the human inducible NO synthase gene were used to prevent ambiguous effects of NO from either exogenous chemical donors or cytokine-stimulated cells. Low concentrations of endogenous NO led to a dose-dependent increase in 6-keto PGF1alpha production (p < 0.05), whereas the highest production of NO resulted in lower 6-keto PGF1alpha production. These data demonstrate a complex regulation of PGHS activity by NO that needs to be considered when proposing a physiological or pathophysiological role for NO.
Davidge
S T
ST
Perinatal Research Centre and Department of Obstetrics and Gynecology, University of Alberta, Edmonton, Canada. sandra.davidge@ualberta.ca
Pitt
B R
BR
McLaughlin
M K
MK
Roberts
J M
JM
Johnson
B A
BA
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D004727:Endothelium / Q000187:drug effects* / Q000378:metabolism; D011464:Epoprostenol / Q000378:metabolism*; D005822:Genetic Vectors; D006147:Guanine / Q000378:metabolism; D006801:Humans; D008168:Lung; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000378:metabolism; D014162:Transfection
D009573:Nitrites; D009569:Nitric Oxide; D015121:6-Ketoprostaglandin F1 alpha; D006147:Guanine; D011464:Epoprostenol; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse