A novel mechanism for vasoconstrictor action of 8-isoprostaglandin F 2α on retinal vessels

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology integrative and comparative physiology, 1998-05, Vol.274 (5), p.R1406-R1416
• Main Authors: Lahaie, Isabelle, Hardy, Pierre, Hou, Xin, Hasséssian, Haroutioun, Asselin, Pierre, Lachapelle, Pierre, Almazan, Guillermina, Varma, Daya R, Morrow, Jason D, Roberts, 2nd, L Jackson, Chemtob, Sylvain
• Format: Article
• Language: English
• ISSN: 0363-6119; 1522-1490
• DOI: 10.1152/ajpregu.1998.274.5.R1406

Using a video-imaging technique, we characterized the effects of 8-isoprostaglandin F (8-iso-PGF ) on retinal vasculature from piglets. 8-Iso-PGF potently contracted (EC = 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 Ca pathway SKF-96365; constrictor effects of 8-iso-PGF were also partly attenuated by the ET -receptor blocker BQ-123 and an inhibitor of endothelin-converting enzyme, phosphoramidon, but was negligibly affected by the L-type voltage-gated Ca channel blocker nifedipine. Correspondingly, 8-iso-PGF elicited endothelin release from retinal preparations, which was markedly reduced by SKF-96365. 8-Iso-PGF also increased thromboxane production in the retina and cultured endothelial cells, but not on retinovascular smooth muscle cells; these effects of 8-iso-PGF were blocked by indomethacin, CGS-12970, SKF-96365, and EGTA, but not by nifedipine. 8-Iso-PGF also increased Ca 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-PGF , stimulated a rise in Ca transients. Finally, H O + FeCl (in vitro) and anoxia followed by reoxygenation (in vivo) stimulated formation of 8-iso-PGF in the retina. In conclusion, 8-iso-PGF -induced retinal vasoconstriction is mediated by cyclooxygenase-generated formation of thromboxane and, to a lesser extent, by endothelin after Ca entry into cells, possibly through receptor-operated channels. Retinal vasoconstriction to 8-isoprostanes might play a role in the genesis of ischemic retinopathies.