Analysis of the pulmonary hypertensive effects of the isoprostane derivative, 8-iso-PGF(2α), in the rat

Gareth W. John, Jean Pierre Valentin

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31 Scopus citations


1. We analysed the pulmonary hypertensive effects of the F2-isoprostane derivative, 8-iso-prostaglandin F(2α) (8-iso-PGF(2α)), in comparison with those of the high efficacy thromboxane A2/prostanoid (TP) receptor agonist, U-46619, in pentobarbitone-anaesthetized, open-chest rats (n = 4-15 per group). 2. 8-iso-PGF(2α) produced dose-dependent increases in mean pulmonary arterial pressure, with an ED50 of 39.0 (31.4-50.6) μg kg-1, i.v. (geometric mean with 95% confidence limits in parentheses) compared to 1.4 (1.1-2.3) μg kg-1, i.v., for U-46619. The maximum responses evoked by U-46619 and 8-iso-PGF(2α) were not statistically significantly different (21.0 ± 1.0 and 25.8 ± 1.9 mmHg at 10 μg kg-1 of U-46619 and 630 μg kg-1 of 8-iso-PGF(2α), respectively). 3. The TP receptor antagonist, SQ 29,548 (0.63 mg kg-1, i.v. + 0.63 mg kg-1 h-1) fully antagonised both U-46619 and 8-iso-PGF(2α)-induced pulmonary hypertensive responses. 4. Further experiments were carried out to determine whether 8-iso-PGF(2α) antagonized the pulmonary hypertensive responses evoked by U-46619, or those induced by itself, as would be predicted for a partial agonist. However, ED10 or ED25 doses of 8-iso-PGF(2α) (10 or 20 μg kg-1, i.v.) failed to reduce the pulmonary hypertensive responses induced either by U-46619 or by itself. 5. The data suggest that in the pulmonary vascular bed of the rat, 8-iso-PGF(2α) acts as an agonist of high intrinsic activity at SQ 29,548-sensitive (probably TP) receptors.

Original languageEnglish
Pages (from-to)899-905
Number of pages7
JournalBritish Journal of Pharmacology
Issue number5
StatePublished - 1997
Externally publishedYes


  • 8-iso-PGF(2α)
  • F-isoprostane
  • Pulmonary hypertension
  • SQ 29,548
  • TP receptor
  • U-46619


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