Dexamethasone inhibits the inducible bioconversion of glyceryl trinitrate to nitric oxide

Vincenzo Mollace, Carolina Muscoli, Michelangelo Iannone, Ernesto Palma, Domenicantonio Rotiroti, Francesco Romeo, Robert Nisticò, Daniela Salvemini

Research output: Contribution to journalArticlepeer-review

Abstract

The aim of this study was to assess the effects of dexamethasone (DEX) on the inducible bioconversion of glyceryl trinitrate (GTN) into nitric oxide in cultured smooth muscle cells, endothelial cells, and the J774 macrophage cell line as well as in vivo and ex vivo in rats either untreated or pretreated with Escherichia coli lipopolysaccharide. In vitro, an increased bioconversion of GTN to nitrite and an elevation of cyclosine guanosine 3,5′-monophosphate (cGMP) levels occurred after treatment with lipopolysaccharide (LPS) (0.5 μg/ml, 18 h). This effect was ablated by co-incubation with DEX (10 μM, 18 h). Rats treated with an intraperitoneal (IP) injection of LPS (4 mg/kg) 18 h beforehand showed enhanced hypotensive responses to GTN (1 mg/kg, intravenously [IV]) and this was prevented when DEX (4 mg/kg, IP) was given together with LPS. Progesterone (50 mg/kg, IP) had no effect on GTN-induced hypotensive response. Conversely, exposure of rat aortic strips obtained from animals pretreated with LPS produced an enhanced vasorelaxant response in LPS-treated rats. Also, this effect was inhibited by pretreatment with DEX. Thus, the induction of the pathway leading to the formation of nitric oxide from GTN is blocked by DEX both in vitro and in vivo, and this may represent a useful tool in the assessment of the enhanced bioconversion of organic nitrates into nitric oxide occurring via inflammatory mechanisms.

Original languageEnglish
Pages (from-to)544-551
Number of pages8
JournalJournal of Cardiovascular Pharmacology
Volume39
Issue number4
DOIs
Publication statusPublished - 2002

Keywords

  • Escherichia coli lipopolysaccharide
  • Nitric oxide
  • Nitrovasodilators
  • Organic nitrates
  • Steroids

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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