Oversø Hansen Pernille, Kringelholt Sidse, Simonsen Ulf, Bek Toke
Department of Ophthalmology, Aarhus University Hospital, Aarhus, Denmark.
Department of Biomedicine, University of Aarhus, Aarhus, Denmark.
Acta Ophthalmol. 2015 Aug;93(5):457-463. doi: 10.1111/aos.12669. Epub 2015 Jan 25.
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.
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), EP1 - (SC-19220), EP2 - (PF-044189) or EP4 receptors (GW627368X). The experiments were repeated after removal of the perivascular retinal tissue.
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 EP4 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.
Hypoxia-induced vasorelaxation of porcine retinal arterioles is mediated by inducible NOS and stimulation of EP4 receptors acting through separate pathways, but mechanisms unrelated to the studied prostaglandin receptors and NOS products are also involved.
研究表明，在抑制前列腺素合成和一氧化氮合酶（NOS）过程中，缺氧诱导的猪视网膜小动脉舒张作用减弱。本研究旨在确定介导此效应的特定前列腺素受体和一氧化氮来源。
将带有保留血管周围视网膜组织的猪视网膜小动脉安装在肌张力测定仪上，并在以下任一种物质存在的情况下暴露于缺氧环境：一氧化氮合酶通用抑制剂L-NAME、诱导型一氧化氮合酶选择性抑制剂1400W、神经元型一氧化氮合酶选择性抑制剂7-硝基吲唑、环氧化酶（COX）通用抑制剂布洛芬或FP-（AL 8810）、DP-（BWA868C）、EP1-（SC-19220）、EP2-（PF-044189）或EP4受体（GW627368X）的拮抗剂。去除血管周围视网膜组织后重复实验。
缺氧诱导带有保留血管周围视网膜组织的视网膜小动脉舒张。在L-NAME、1400W、布洛芬和EP4受体拮抗剂GW627368X存在的情况下，这种舒张作用显著减弱。与单独使用这些化合物的效果相比，同时添加L-NAME或1400W与布洛芬，但不与GW627368X联合使用，可叠加性降低缺氧诱导的血管舒张。
缺氧诱导的猪视网膜小动脉血管舒张由诱导型一氧化氮合酶介导，EP4受体通过不同途径发挥刺激作用，但也涉及与所研究的前列腺素受体和一氧化氮合酶产物无关的机制。
