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 va rious cell types, but reports conflict in regard to its stimulatory versus inhibitory role. Murine lung endothelial cells infected with a retroviral v ector expressing the human inducible NO synthase gene were used to prevent ambiguous effects of NO from either exogenous chemical donors or cytokine-s timulated cells. Low concentrations of endogenous NO led to a dose-dependen t increase in 6-keto PGF(1 alpha) production (p < 0.05), whereas the highes t production of NO resulted in lower 6- keto PGF(1 alpha) production. These data demonstrate a complex regulation of PGHS activity by NO that needs to be considered when, proposing a physiological or pathophysiological role f or NO. (C) 1999 Elsevier Science Inc. All rights reserved.