Perivascular Cells With Pericyte Characteristics Are Involved in ATP- and PGE2-Induced Relaxation of Porcine Retinal Arterioles In Vitro

PURPOSE. Relaxation of porcine retinal arterioles in vitro has been shown to be preceded by calcium activity in a population of perivascular cells that cannot be classified as neurons, glial cells, or vascular smooth muscle cells. The purpose of the present investigation was to study calcium activity in these perivascular cells during ATP- and PGE2-induced vasorelaxation, and to identify pericyte markers and other cellular constituents characterizing these cells. METHODS. Porcine arterioles were loaded with a calcium-sensitive fluorophore and mounted in a myograph. Simultaneous measurements of calcium activity and vascular tone during stimulation with ATP and PGE(2) were performed before and after addition of specific antagonists to these compounds and to nitric oxide. Additionally, immunohistochemistry was performed on whole mounts of porcine retina using antibodies to known markers of vascular pericytes and cellular components of the vascular wall. RESULTS. Relaxation of retinal arterioles with both ATP and PGE(2) was preceded by a significant increase in the number of perivascular cells displaying calcium activity. The effect of ATP was inhibited by the adenosine receptor antagonist 8-PSPT, whereas the effect of PGE(2) was inhibited by the EP1 receptor antagonist SC19220 and the NO-synthesis inhibitor L-NAME. The perivascular cells had morphological features in common with pericytes and displayed immunoreactivity to the pericyte markers NG2 and CD-13, but not to markers of glial cells, neurons, or vascular smooth muscle cells. CONCLUSIONS. The perivascular cell type located external to the smooth muscle cells in porcine retinal arterioles shows calcium activity during relaxation with ATP and PGE2 and has morphological properties in common with pericytes. Future studies should focus on the role of this cell type for regulating retinal blood flow and for retinal vascular disease.