Urinary excretion of thromboxane and prostacyclin metabolites during chronic low-dose aspirin: evidence for an extrarenal origin of urinary thromboxane B2 and 6-keto-prostaglandin F1α in healthy subjects

Chiara Chiabrando, Luigi Rivoltella, Luciana Martelli, Sandro Valzacchi, Roberto Fanelli

Research output: Contribution to journalArticlepeer-review

Abstract

In vivo biosynthesis of thromboxane and prostacyclin is currently evaluated by measuring urinary excretion of selected metabolites. Urinary thromboxane B2 (TXB2) and 6-keto-prostaglandin F1α (6-keto-PGF1α) (non-enzymatic hydrolysis products of thromboxane and prostacyclin) are thought to derive from renal biosynthesis of the parent compounds, while enzymatic metabolites such as 2,3-dinor-TXB2 and 2,3-dinor-6-keto-PGF1α appear to be mainly derived from systemic (platelet) thromboxane and (vascular) prostacyclin, respectively. Using immunoaffinity extraction and high-resolution gas chromatography-negative ion chemical ionization mass spectrometry (HRGC-NICIMS), we measured the paired excretion of non-enzymatic and enzymatic metabolites of thromboxane and prostacyclin in healthy subjects before, during and after an eight-day schedule of oral low-dose aspirin (30 mg/day), a treatment known to inhibit platelet and perhaps vascular but not renal cyclooxygenase. Low-dose aspirin cumulatively reduced urinary excretion of TXB2 and 2,3-dinor-TXB2 (about 80% inhibition on day 8 of aspirin treatment, P <0.01), as well as 6-keto-PGF1α and 2,3-dinor-6-keto-PGF1α (about 45% inhibition on day 8 of aspirin treatment, P <0.01). Excretion of all metabolites recovered slowly after aspirin withdrawal. Urinary PGE2, taken as an index of renal cyclooxygenase activity, was not inhibited by aspirin. A highly significant correlation was found between paired excretion values of non-enzymatic vs. enzymatic metabolites of thromboxane and prostacyclin in all individuals studied (TXB2 vs. 2,3-dinor-TXB2 (r = 0.91 ± 0.03); 6-keto-PGF1α vs. 2,3-dinor-6-keto-PGF1α (r = 0.92 ± 0.06)), irrespective of aspirin treatment. TXB2/2,3-dinor-TXB2 and 6-keto-PGF1α/2,3-dinor-6-keto-PGF1α mean ratios remained unchanged throughout the experiment. These data do not support the view that urinary TXB2 and 6-keto-PGF1α derive mainly from renal biosynthesis in healthy subjects, but rather suggest that they may represent a fraction of systemic (platelet) thromboxane and (vascular) prostacyclin escaping metabolism. These data also suggest that chronic low-dose aspirin may partly inhibit vascular prostacyclin in addition to platelet thromboxane biosynthesis.

Original languageEnglish
Pages (from-to)247-254
Number of pages8
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1133
Issue number3
DOIs
Publication statusPublished - Feb 3 1992

Keywords

  • Aspirin
  • Gas chromatography-mass spectrometry
  • Immuno-affinity
  • Kidney
  • Platelet
  • Prostaglandin E
  • Protacyclin
  • Thromboxane
  • Urine
  • Vessel

ASJC Scopus subject areas

  • Biophysics
  • Cell Biology
  • Molecular Biology

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