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Hypoxia‐induced relaxation of porcine retinal arterioles in vitro depends on inducible NO synthase and EP 4 receptor stimulation in the perivascular retina
Author(s) -
Oversø Hansen Pernille,
Kringelholt Sidse,
Simonsen Ulf,
Bek Toke
Publication year - 2015
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/aos.12669
Subject(s) - retinal , nitric oxide synthase , prostaglandin e2 receptor , receptor , chemistry , hypoxia (environmental) , stimulation , prostaglandin , myograph , retina , cyclooxygenase , receptor antagonist , nitric oxide , endocrinology , antagonist , biology , biochemistry , agonist , enzyme , neuroscience , organic chemistry , oxygen
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 i NOS inhibitor 1400W, the selective n NOS inhibitor 7‐nitroindazole, the general cyclooxygenase ( COX ) inhibitor ibuprofen or an antagonist to the FP ‐ ( AL 8810), DP ‐ ( BWA 868C), EP 1 ‐ ( SC ‐19220), EP 2 ‐ ( PF ‐044189) or EP 4 receptors ( GW 627368X). 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 GW 627368X. The simultaneous addition of L‐ NAME or 1400W in combination with ibuprofen, but not GW 627368X, 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.