Ca²⁺ signaling in perivascular cells during PGE₂-induced relaxation and PGF_2α-induced contraction of porcine retinal arterioles in vitro

Abstract

Purpose: Recently, a novel population of perivascular cells (PVC) located immediately external to the vascular smooth muscle cells of the retinal arterioles has been identified. PVCs may contribute to agonist-induced modulation of retinal arterioles tone, and the purpose of the present study was to identify the source of Ca²⁺ recruitment in the perivascular cells during PGE₂-induced relaxation and PGF_2α-induced contraction of porcine retinal arterioles.

Methods: Porcine retinal arterioles with preserved perivascular retinal tissue were mounted in a confocal myograph and loaded with the Ca²⁺-sensitive fluorophore Oregon Green. After either pre-constriction with U46619 (10^-6 M) followed by the addition of the relaxing prostaglandin PGE₂ (10^-5 M) or addition of the constricting prostaglandin PGF_2α (10^-5 M) arteriolar tone and fluorescence from PVCs were recorded simultaneously with and without the presence of Ca²⁺ channel blockers (ryanodine, nifedipine, LOE908, CPA, 2-APB).

Results: The addition of PGE₂ induced arteriolar relaxation and none of the Ca²⁺ channel blockers caused significant changes in this relaxation. Both PGE₂ and PGF_2α increased Ca²⁺ activity in the PVCs. CPA and 2-APB reduced the number of PVCs displaying Ca²⁺ activity after stimulation with both compounds, whereas ryanodine, nifedipine and LOE908 reduced calcium acitivity in PVCs stimulated with PGF_2α.

Conclusions: PGE₂ and PGF_2α induce Ca²⁺ activity in perivascular cells of porcine retinal arterioles, and sarcoplasmic reticulum and inositol triphosphate receptors are important sources of this Ca²⁺ signal. A coupling between PGE₂-induced relaxation and Ca²⁺ recruitment in perivascular retinal cells is uncertain.