Differential effects of purines and prostaglandins on hypoxia induced dilatation of porcine retinal vessels at different branching level ex vivo

Abstract

The metabolic pathways leading from hypoxia to retinal vasodilatation can involve effects of both purines and prostaglandins, but the effects of these compounds at different vascular branching levels are unknown. The purpose of the present study was to investigate differential effects of purines and prostaglandins in hypoxia-induced dilatation of retinal arterioles, precapillary arterioles and capillaries ex vivo.Porcine hemiretinas were mounted in a tissue chamber while monitoring temperature, pH, and oxygen tension. The effect of hypoxia on the diameter of larger arterioles, precapillary arterioles and capillaries was studied in the presence of the ecto-nucleotidase inhibitor AOPCP, the nonselective P2 purinoreceptor antagonist PPADS, the A2B adenosine receptor antagonist MRS 1754, the A3 adenosine receptor antagonist MRS 1523, the EP1 receptor antagonist SC-19220, the EP2 receptor antagonist PF-04418948, the EP3 receptor antagonist L-798,106, the EP4 receptor antagonist L-161-982, the prostaglandin synthesis inhibitor ibuprofen, and ibuprofen combined with AOPCP or ATP.Hypoxia-induced dilatation in arterioles was reduced by the A2B adenosine receptor antagonist (p < 0.01) and increased by the EP2 and the EP3 receptor antagonists (p < 0.01 for both comparisons). In precapillary arterioles the dilatation was reduced by the EP2 receptor antagonist (p < 0.04) and increased by the EP1 receptor antagonist (p < 0.03), whereas in capillaries the dilatation was increased by both the A3 adenosine receptor antagonist (p < 0.01), by ibuprofen in combination with the unspecific ecto-nucleotidase inhibitor AOPCP (p = 0.04) and by the prostaglandin EP3 receptor antagonist.Hypoxia-induced dilatation of retinal vessels is influenced by adenosine A2B and A3 receptors, and by the prostaglandin EP1, EP2 and EP3 receptors. The effects mediated by these receptors differ at different branching levels of the resistance vessels.