Abstract 977: Regenerated Endothelial Cells Produce Vasoconstrictive Prostanoid(s) rather than Vasodilative Prostanoid(s) through COX-1 and COX-2 Dependent Pathways
The purpose of this study was to clarify endothelial functions of regenerated endothelial cells after endothelial injury. The endothelial injury of right femoral artery in Wistar rats was induced by photochemical reaction with rose Bengal and 540nm-light irradiation. Following the precontraction with phenylephrine, acetylcholine (ACh, 10−10–10−4 M) induced vasodilation in the right femoral injured artery (IA) as well as the sham-operated left femoral artery (SA) was assessed by an isometric transducer. Although ACh-induced vasodilatation was abolished in IA one day after the injury, sodium nitroprusside-induced endothelium-independent relaxations were identical in IA and SA. Maximal relaxation caused by ACh was completely recovered in IA after 2 weeks. However, L-NAME (10−4 M)-sensitive NO-mediated portion of ACh-induced relaxations was reduced in IA (55 +/− 12 %) compared with SA (81 +/− 9 %) (n=21, p<0.05), while KCl (40 mM)-sensitive EDHF-mediated relaxations were much more pronounced in IA than SA. Treatment with indomethacin (10−4 M) with L-NAME attenuated ACh-induced relaxations by 9 +/− 7 % in SA, while it enhanced ACh-induced relaxations by 19 +/− 7 % in IA (p<0.05). A cyclooxygenase (COX)-1 inhibitor SC-560, a COX-2 inhibitor NS-398, and a prostaglandin F2 alpha receptor antagonist AL-8810 mimicked the effect of indomethacin. However, a thromboxane synthetase inhibitor OKY-046 did not affect ACh-induced relaxation in SA. These results for the first time demonstrated that regenerated endothelial cells produce vasoconstrictive prostanoid PGF2 alpha rather than vasodilative prostanoid through COX-1 and 2 dependent pathways.