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双嘧达莫对猪睫状动脉血管反应的影响。

Effect of dipyridamole on vascular responses of porcine ciliary arteries.

作者信息

Meyer P, Flammer J, Lüscher T F

机构信息

Department of Research, University Eye Hospital, Basel, Switzerland.

出版信息

Curr Eye Res. 1996 Apr;15(4):387-93. doi: 10.3109/02713689608995829.

Abstract

This study investigated the effects of dipyridamole in isolated porcine ciliary arteries (diameter 200-250 microns). Isolated porcine ciliary arteries were suspended in myograph chambers filled with modified Krebs-Ringer solution (37 degrees C; 95% O2/5% CO2) for isometric tension recording. Dipyridamole induced concentration-dependent relaxations of porcine ciliary arteries with endothelium precontracted with thromboxane analogue U-46619 (10(-6)M), KCl (50 mM), or endothelin-1 (10(-8)M). Removal of the endothelium of the ciliary vessels and preincubation of the arteries with L-NAME (10(-5)M), or indomethacin (10(-5)M), or the combination of the two drugs significantly reduced the relaxation to dipyridamole (p = 0.002-0.03). Similar vascular responses could be observed in a time-dependent analysis of the effect of a single concentration dipyridamole (10(-4)M). The stimulator of cAMP forskolin also caused relaxations. Endothelin-1 (10(-12)-10(-7)M) and U-46619 (10(-10)-10(-6)M) induced potent contractions of porcine ciliary arteries. Preincubation with dipyridamole (10(-5)M) reduced contractions to endothelin-1 as compared to control (p < 0.004), while contractions to U-46619 were only slightly affected under these conditions (n.s.). These findings demonstrate that dipyridamole is a vasodilator in porcine ciliary arteries. Endothelial nitric oxide and prostacyclin contribute importantly to the effects of dipyridamole. Further studies are required to show whether these properties of dipyridamole may also occur in vivo and offer clinical use in patients with ocular vasospasms and other ophthalmic vascular dysfunctions.

摘要

本研究调查了双嘧达莫对离体猪睫状动脉(直径200 - 250微米)的影响。将离体猪睫状动脉悬挂于充满改良克雷布斯-林格溶液(37℃;95% O₂/5% CO₂)的肌张力测定仪小室中,进行等长张力记录。双嘧达莫可使预先用血栓素类似物U - 46619(10⁻⁶M)、氯化钾(50 mM)或内皮素-1(10⁻⁸M)预收缩的猪睫状动脉产生浓度依赖性舒张。去除睫状血管内皮,并用L - 精氨酸甲酯(10⁻⁵M)、吲哚美辛(10⁻⁵M)或两种药物联合预处理动脉,可显著降低对双嘧达莫的舒张反应(p = 0.002 - 0.03)。在对单一浓度双嘧达莫(10⁻⁴M)作用的时间依赖性分析中可观察到类似的血管反应。环磷酸腺苷刺激剂福斯可林也可引起舒张。内皮素-1(10⁻¹² - 10⁻⁷M)和U - 46619(10⁻¹⁰ - 10⁻⁶M)可引起猪睫状动脉强烈收缩。与对照组相比,用双嘧达莫(10⁻⁵M)预处理可降低对内皮素-1的收缩反应(p < 0.004),而在这些条件下对U - 46619的收缩反应仅略有影响(无统计学意义)。这些发现表明双嘧达莫是猪睫状动脉的血管舒张剂。内皮源性一氧化氮和前列环素对双嘧达莫的作用起重要作用。需要进一步研究以表明双嘧达莫的这些特性是否也会在体内出现,并为眼部血管痉挛和其他眼科血管功能障碍患者提供临床应用。

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