A common pathway for nitric oxide release from NO-aspirin and glyceryl trinitrate

Nina Grosser, Henning Schröder

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

NO-Aspirin (NCX-4016) releases nitric oxide (NO) in biological systems through as yet unidentified mechanisms. In LLC-PK1 kidney epithelial cells, a 5-h pretreatment with glyceryl tinitrate (GTN, 0.1-1 μM) significantly attenuated the cyclic GMP response to a subsequent challenge with both NO-aspirin or GTN. Similarly, NO-aspirin (10-100 μM) was found to induce tolerance to its own cyclic GMP stimulatory action and to that of GTN. In contrast, cyclic GMP stimulation by the spontaneous NO donor SIN-1, which releases NO independently of enzymatic catalysis, remained unimpaired in cells pretreated with GTN or NO-aspirin. The observed cross-tolerance between NO-aspirin and GTN cells indicates that bioactivation pathways of organic nitrates, which have been shown to involve cytochrome P450, may also be responsible for NO release from NO-aspirin. Prolonged treatment with NO-aspirin causes down-regulation of the cellular cyclic GMP response, suggesting that tolerance may occur during therapy with NO-aspirin. (C) 2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)255-258
Number of pages4
JournalBiochemical and Biophysical Research Communications
Volume274
Issue number1
DOIs
StatePublished - Jul 21 2000

Keywords

  • Aspirin
  • Cultured cells
  • Glyceryl trinitrate
  • Linsidomine
  • Nitrate tolerance
  • Nitric oxide
  • Nitric oxide donor
  • Nonsteroidal anti-inflammatory drugs
  • SIN-1
  • cGMP

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