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 findings 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.
Inoue
T
T
Department of Geriatric Medicine, Osaka University Medical School, Japan.
Fukuo
K
K
Morimoto
S
S
Koh
E
E
Ogihara
T
T
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism*; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D007700:Kinetics; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000494:pharmacology; D013997:Time Factors; D019323:omega-N-Methylarginine
D007375:Interleukin-1; D011994:Recombinant Proteins; D009599:Nitroprusside; D019323:omega-N-Methylarginine; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D001120:Arginine; D013482:Superoxide Dismutase; D006152:Cyclic GMP; D015232:Dinoprostone