Yoshitomi Takeshi, Yamaji Kazutsuna, Ishikawa Hitoshi, Ohnishi Yoshitaka
Department of Ophthalmology, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-0012, Japan.
Exp Eye Res. 2002 Dec;75(6):669-76. doi: 10.1006/exer.2002.2061.
Nipradilol is a new antiglaucoma ophthalmic agent used in Japan. Topical application of nipradilol is reported to increase ocular blood flow. To investigate the action of this drug, we studied the effect of nipradilol on the isolated rabbit ciliary artery. Under the dissecting microscope, ciliary arteries were prepared from rabbit eyes and mounted on a myograph system. The effects of nipradilol on the isolated rabbit ciliary artery were investigated using isometric tension recording methods. Nipradilol provoked a dose-dependent (10 microM-1m M) relaxation in ciliary arteries that were pre-contracted with high-K solutions (K(+): 100.7 m M). It also inhibited the amplitude of smooth muscle contraction evoked by field stimulation. Nipradilol was more effective in relaxing phenylephrine-induced contraction (EC(50): 21.6+/-16.3 microM) compared to high-K solution-induced contractions (EC(50): 230+/-130 microM). Application of N(w)-nitro- L -arginine methylester (300 microM), a nitric oxide (NO) synthase inhibitor, or denudations of endothelium by rubbing the inner surface with a scalp hair did not affect this relaxation. However, NO scavenger carboxy-PTIO (1m M) or methylene blue (10 microM), a guanylate cyclase inhibitor, inhibited the nipradilol-induced relaxation. These results indicate that nipradilol relaxes the rabbit ciliary artery by two different mechanisms. First, the relaxation is due to the NO produced by denitrification of nipradilol itself. Second, nipradilol may act as an alpha-adrenergic antagonist. These actions of nipradilol may explain the mechanisms of increased ocular blood flow in vivo.
尼普地洛是一种在日本使用的新型抗青光眼眼科药物。据报道，局部应用尼普地洛可增加眼部血流量。为了研究这种药物的作用，我们研究了尼普地洛对离体兔睫状动脉的影响。在解剖显微镜下，从兔眼中分离出睫状动脉，并安装在肌动描记系统上。使用等长张力记录方法研究了尼普地洛对离体兔睫状动脉的影响。尼普地洛可使预先用高钾溶液（K⁺：100.7 mM）预收缩的睫状动脉产生剂量依赖性（10 μM - 1 mM）舒张。它还抑制了场刺激引起的平滑肌收缩幅度。与高钾溶液诱导的收缩（EC₅₀：230 ± 130 μM）相比，尼普地洛在舒张去氧肾上腺素诱导的收缩方面更有效（EC₅₀：21.6 ± 16.3 μM）。应用一氧化氮（NO）合酶抑制剂Nⁿ-硝基-L-精氨酸甲酯（300 μM）或用头皮毛发摩擦内表面使内皮剥脱并不影响这种舒张。然而，NO清除剂羧基-PTIO（1 mM）或鸟苷酸环化酶抑制剂亚甲蓝（10 μM）可抑制尼普地洛诱导的舒张。这些结果表明，尼普地洛通过两种不同机制使兔睫状动脉舒张。首先，舒张是由于尼普地洛自身脱硝化产生的NO。其次，尼普地洛可能作为一种α-肾上腺素能拮抗剂起作用。尼普地洛的这些作用可能解释了体内眼部血流量增加的机制。
