ATP-Induced Relaxation of Porcine Retinal Arterioles In Vitro Depends on Prostaglandin E Synthesized in the Perivascular Retinal Tissue

PURPOSE. It has been shown that inhibition of prostaglandin synthesis in the perivascular retinal tissue can prevent the relaxation of retinal arterioles induced by N-methyl-D-aspartic acid (NMDA) and adenosine triphosphate (ATP). The purpose of the present study was to identify the prostaglandins involved in this retina-dependent relaxation. METHODS. Porcine retinal arterioles were mounted in a myograph for isometric tone measurements. The effect of the prostaglandins (PGs) PGE(2), PGF(2 alpha), PGD(2), and PGI(2) and of thromboxane A(2) (TXA(2)) on vascular tone was recorded before and after removal of the perivascular retina, and the specificity of the responses were confirmed by blocking with specific antagonists. Finally, the coupling between prostaglandins found to have a specific vasoactive effect, dependent on the perivascular retina, and the individual vasorelaxing effects of NMDA, ATP, and adenosine were studied. RESULTS. All prostaglandins tested showed a significant relaxation of precontracted arterioles at the highest concentrations, whereas PGF(2 alpha) induced a significant constriction of isolated noncontracted arterioles. In the presence of perivascular retinal tissue, the dilating effect of PGE(2) increased significantly, an effect that was blocked by a prostaglandin E prostanoid (EP(1)) receptor blocker, whereas PGD(2) induced a dual response, with a significant contraction at low concentrations and a significant dilation at high concentrations. Inhibition of the cyclo-oxygenase (COX) enzyme with ibuprofen, as well as the EP(1) receptor, blocked the vasodilating effect of ATP, but not that of NMDA and adenosine, in the presence of perivascular retinal tissue. CONCLUSIONS. ATP-induced vasodilation depends on the production of PGE in the perivascular retina. However, the regulation of retinal arteriolar tone involves COX products other than PGE. (Invest Ophthalmol Vis Sci. 2010;51:5168-5175) DOI:10.1167/iovs.09-4608