A novel mechanism for vasoconstrictor action of 8-isoprostaglandin F2 alpha on retinal vessels

Am J Physiol. 1998 May;274(5):R1406-16. doi: 10.1152/ajpregu.1998.274.5.R1406.


Using a video-imaging technique, we characterized the effects of 8-isoprostaglandin F2 alpha (8-iso-PGF2 alpha) on retinal vasculature from piglets. 8-Iso-PGF2 alpha potently contracted (EC50 = 5.9 +/- 0.5 nM) retinal vessels. These effects were completely antagonized by the cyclooxygenase inhibitor indomethacin, the thromboxane synthase blocker CGS-12970, the thromboxane receptor antagonist L-670596, and the putative inhibitor of the non-voltage-dependent receptor-operated Ca2+ pathway SKF-96365; constrictor effects of 8-iso-PGF2 alpha were also partly attenuated by the ETA-receptor blocker BQ-123 and an inhibitor of endothelin-converting enzyme, phosphoramidon, but was negligibly affected by the L-type voltage-gated Ca2+ channel blocker nifedipine. Correspondingly, 8-iso-PGF2 alpha elicited endothelin release from retinal preparations, which was markedly reduced by SKF-96365. 8-Iso-PGF2 alpha also increased thromboxane production in the retina and cultured endothelial cells, but not on retinovascular smooth muscle cells; these effects of 8-iso-PGF2 alpha were blocked by indomethacin, CGS-12970, SKF-96365, and EGTA, but not by nifedipine. 8-Iso-PGF2 alpha also increased Ca2+ transients in retinal endothelial cells, which were inhibited by SKF-96365 and EGTA, but not by nifedipine, whereas in smooth muscle cells U-46619, but not 8-iso-PGF2 alpha, stimulated a rise in Ca2+ transients. Finally, H2O2 + FeCl2 (in vitro) and anoxia followed by reoxygenation (in vivo) stimulated formation of 8-iso-PGF2 alpha in the retina. In conclusion, 8-iso-PGF2 alpha-induced retinal vasoconstriction is mediated by cyclooxygenase-generated formation of thromboxane and, to a lesser extent, by endothelin after Ca2+ entry into cells, possibly through receptor-operated channels. Retinal vasoconstriction to 8-isoprostanes might play a role in the genesis of ischemic retinopathies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism
  • Dinoprost / analogs & derivatives*
  • Dinoprost / pharmacology
  • F2-Isoprostanes
  • Retinal Vessels / drug effects*
  • Retinal Vessels / physiology*
  • Signal Transduction / physiology*
  • Swine
  • Vasoconstriction / drug effects*
  • Vasoconstriction / physiology*
  • Vasoconstrictor Agents / pharmacology*


  • F2-Isoprostanes
  • Vasoconstrictor Agents
  • 8-epi-prostaglandin F2alpha
  • Dinoprost
  • Calcium