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T Yoshitomi, K Yamaji, H Ishikawa, Y Ohnishi; Vasodilative Effects of Nipradilol, an Alpha- and Beta- Adrenergic Blocker With Nitric Oxide Donator Action, in Rabbit Ciliary Artery . Invest. Ophthalmol. Vis. Sci. 2002;43(13):300.
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Purpose: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. Methods:Under the dissecting microscope, ciliary arteries were prepared from rabbit eyes and mounted in a myograph system. The effects of nipradilol on the isolated rabbit ciliary artery were investigated using isometric tension recording methods. Results: Nipradilol provoked a dose-dependent (10 µM to 1 mM) relaxation in ciliary arteries that were pre-contracted with high-K solutions (118mM). It also inhibited the amplitude of smooth muscle contraction evoked by field stimulation. Nipradilol was more effective in relaxing phenylephrine-induced contraction (EC50: 21.6 ± 16.3 µM) compared to high-K solution induced contractions (EC50: 231 ± 132 µM). Application of NG-nitro-L-arginine methylester (300 µM), a nitric oxide (NO) synthase inhibitor, or denudations of endothelium by rubbing the inner surface with a scarp hair did not affect this relaxation. However, NO scavenger carboxy-PTIO (1 mM) or methyleneblue (10 µM), a guanylate cyclase inhibitor, inhibited the nipradilol-induced relaxation. Conclusion:These results indicate that nipradilol relaxes the rabbit ciliary artery by two different mechanisms. First, the relaxation is due to the nitric oxide produced by denitrification of nipradilol itself. Second, nipradilol may act as an alpha1-adrenergic antagonist. These actions of nipradilol may explain the mechanisms of increased ocular blood flow in vivo.
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