Hypoxia-induced relaxation of porcine retinal arterioles in vitro depends on prostaglandins and NO and the presence of perivascular retinal tissue, whereas recovery of tone after hypoxia depends on the action of prostaglandins. Clinical intervention studies of these effects may help treating retinal diseases where disturbances in tissue oxygenation are involved in the disease pathogenesis.
ABSTRACT.Purpose: Hypoxia-induced relaxation of porcine retinal arterioles has been shown to be reduced during inhibition of prostaglandin synthesis and nitric oxide synthase (NOS). The purpose of this study was to identity the specific prostaglandin receptor(s) and source(s) of NO mediating this effect. Methods: Porcine retinal arterioles with preserved perivascular retinal tissue were mounted in a myograph and were exposed to hypoxia in the presence of one of the following: the general NO synthase inhibitor L-NAME, the selective iNOS inhibitor 1400W, the selective nNOS inhibitor 7-nitroindazole, the general cyclooxygenase (COX) inhibitor ibuprofen or an antagonist to the FP-(AL 8810), DP-(BWA868C), EP 1 -(SC-19220), EP 2 -(PF-044189) or EP 4 receptors (GW627368X). The experiments were repeated after removal of the perivascular retinal tissue. Results: Hypoxia induced relaxation of retinal arterioles with preserved perivascular retinal tissue. This relaxation was significantly reduced in the presence of L-NAME, 1400W, ibuprofen and the EP 4 receptor antagonist GW627368X. The simultaneous addition of L-NAME or 1400W in combination with ibuprofen, but not GW627368X, reduced hypoxia-induced vasorelaxation additively as compared to the effect of the compounds individually. Conclusion: Hypoxia-induced vasorelaxation of porcine retinal arterioles is mediated by inducible NOS and stimulation of EP 4 receptors acting through separate pathways, but mechanisms unrelated to the studied prostaglandin receptors and NOS products are also involved.
ABSTRACT.Purpose: Prostaglandin analogues are used to reduce the intraocular pressure (IOP) in glaucoma, but also affect the tone of the arteries supplying the ciliary body. Previously, the effect of prostaglandins has been studied on the extraocular ciliary arteries, whereas the effect on intraocular ciliary arteries has not been studied in detail. Methods: Intraocular long posterior porcine ciliary arteries were isolated and mounted in a myograph system for isometric tension recording, and the effects of PGF 2a , the prostaglandin analogue latanoprost, PGD 2 , PGE 2 , PGI 2 and the thromboxane analogue U46619 were studied in the presence and absence of selective receptor antagonists. Results: The prostaglandins PGD 2 and PGE 2 induced relaxation at low concentrations (10 )9 -3 · 10 )7 m), which could be inhibited by blocking either the DP or the EP 4 receptor, whereas PGD 2 , PGE 2 , PGF 2a , latanoprost and U46619 induced contraction at high concentrations (10 )6 -10 )5 m), which could be inhibited by blocking the TP receptor. Additionally, blocking of the FP receptor induced a right-shift of latanoprost-induced contraction. Conclusions: Prostaglandins with affinity to DP 1 and EP 4 receptors induce relaxation at low concentrations, and prostaglandins with affinity to TP and FP receptors induce contraction at high concentrations of intraocular porcine ciliary vessels in vitro. The findings may contribute to understanding the regulation of blood flow to the ciliary body.
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