Intravenously administered phosphodiesterase 4 inhibitors dilate retinal blood vessels in rats.
Intravenously administered phosphodiesterase 4 inhibitors dilate retinal blood vessels in rats.
复制标题
静脉注射磷酸二酯酶 4 抑制剂可扩张大鼠视网膜血管。
DOI：
10.1016/j.ejphar.2008.10.060
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发表时间：
2009
影响因子：
5
通讯作者：
K. Ishii
中科院分区：
文献类型：
--
作者：
T. Miwa;A. Mori;T. Nakahara;K. Ishii
在本研究中，我们检查了静脉内给予磷酸二酯酶4抑制剂（咯利普兰和4-（3-丁氧基-4-甲氧基苄基）-2-咪唑啉酮（Ro-20-1724））和非选择性磷酸二酯酶抑制剂（茶碱）对大鼠视网膜血管直径和眼底（视网膜/脉络膜）血流的影响。雄性Wistar大鼠（8- 10周龄）用河豚毒素（50 μg/kg，i. v.）以消除任何神经活动并防止人工通气下的眼球运动。甲氧胺用于维持充分的体循环。眼底图像是用原始的高分辨率数字眼底照相机拍摄的小动物。使用个人计算机上的图像处理软件测量数字图像中包含的视网膜血管的直径。使用激光多普勒流量计测量眼底血流。两种咯利普兰（0.01-10 μg/kg/min，i. v.）和Ro-20-1724（0.01-10 μg/kg/min，i.v.）以剂量依赖性方式增加视网膜血管直径，对全身血压、心率和眼底血流无显著影响。磷酸二酯酶4抑制剂对视网膜小动脉的作用大于对视网膜小静脉的作用。类似地，茶碱（0. l-lOmg/kg/min，i. v.）扩张视网膜血管，而它降低血压和增加心率显着。这些结果表明，磷酸二酯酶4有助于维持视网膜血管张力。磷酸二酯酶4抑制剂可被认为是治疗视网膜循环障碍相关疾病而无严重心血管副作用的候选药物。
In the present study, we examined effects of intravenously administered inhibitors of phosphodiesterase 4 (rolipram and 4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone (Ro-20-1724)) and non-selective inhibitor of phosphodiesterases (theophylline) on diameter of retinal blood vessel and fundus (retinal/choroidal) blood flow in rats. Male Wistar rats (8- to 10-week-old) were treated with tetrodotoxin (50 μg/kg, i.v.) to eliminate any nerve activity and prevent the eye movement under artificial ventilation. Methoxamine was used to maintain adequate systemic circulation. Ocular fundus images were captured with an original high-resolution digital fundus camera for small animals. Diameters of retinal blood vessels contained in the digital images were measured using image-processing softwares on a personal computer. Fundus blood flow was measured using a laser Doppler flow meter. Both rolipram (0.01–10 μg/kg/min, i.v.) and Ro-20-1724 (0.01–10 μg/kg/min, i.v.) increased diameters of retinal blood vessels in a dose-dependent manner without significant effect on systemic blood pressure, heart rate and fundus blood flow. The effects of phosphodiesterase 4 inhibitors on retinal arterioles were greater than those on retinal venules. Similarly, theophylline (0.1–10 mg/kg/min, i.v.) dilated retinal blood vessels, whereas it decreased blood pressure and increased heart rate markedly. These results suggest that phosphodiesterase 4 contributes to maintenance of retinal vascular tone. Inhibitors of phosphodiesterase 4 could be considered as a candidate for therapeutic drugs to treat diseases associated with disorders of retinal circulation without severe cardiovascular side-effects.
影响因子：
4.8
作者：
Bing Sun;Haiquan Li;Y. Shakur;J. Hensley;S. Hockman;J. Kambayashi;V. Manganiello;Yongge Liu
通讯作者：
Bing Sun;Haiquan Li;Y. Shakur;J. Hensley;S. Hockman;J. Kambayashi;V. Manganiello;Yongge Liu