NITRIC-OXIDE MEDIATES INTERLEUKIN-1-INDUCED PROSTAGLANDIN-E2 PRODUCTION BY VASCULAR SMOOTH-MUSCLE CELLS

We examined the possible participation of nitric oxide (NO) in the activation of cyclooxygenase, a heme-containing enzyme, induced by interleukin-1 (IL-1) in vascular smooth muscle cells (VSMC). IL-1 induced a delayed and prolonged release of both NO and prostaglandin E2 (PGE2) from VSMC. NG-monomethyl-L-arginine (L-NMMA), an inhibitor of NO synthesis, partially but significantly inhibited the PGE2 release induced by IL-1, whereas it completely inhibited the IL-1-induced NO production. The inhibitory effects of L-NMMA on IL-1-induced production of both NO and PGE2 were partially reversed by a 10-fold excess of L-arginine. In addition, coincubation with superoxide dismutase enhanced the IL-1-induced PGE2 release from VSMC. In contrast, 8-bromo-cyclic GMP did not stimulate PGE2 release. Furthermore, 0.2 mM sodium nitroprusside directly stimulated PGE2 release from VSMC. These lindings suggest that NO at least in part mediates the IL-1-induced PGE2 production, and that NO may be one of the important signals for the activation of cyclooxygenase to produce PGE2 in VSMC. © 1993 Academic Press.