Vasodilatory Mechanism of Levobunolol on Isolated Rabbit Ciliary Artery

Abstract

Abstract: : Purpose: Topical application of levobunolol, a beta antagonist used for treatment of glaucoma, is reported to increase ocular blood flow. To investigate the vasodilatory mechanism of this drug, we have investigated the effect of this drug on isolated rabbit ciliary artery in vitro. Methods: Under the dissecting microscope, ciliary arteries were prepared from albino rabbit eyes and mounted in a myograph system. The effects of levobunolol and other agents were investigated using isometric tension recording methods. Results: Levobunolol induced a dose–dependent relaxation in ciliary arteries that were pre–contracted with high–K solution, 10µM histamine, 10µM phenylephrine or 100nM endothelin–1. Levobunolol was more effective in relaxing histamine–induced contraction (EC₅₀: 20.6±16.3 µM) compared to high–K solution induced contractions (EC₅₀: 80.3±12.6 µM). Application of N^G–nitro–L–arginine methylester (300µM), a nitric oxide (NO) synthase inhibitor, or denudations of endothelium by rubbing the inner surface with a scarp hair did not affect this relaxation. Pretreatment with levobunolol (100 µM) inhibited histamine–induced transient contractions in Ca²⁺–free solution by 48.2±14.6 %. Conclusions: Levobunolol relaxed pre–contracted rabbit ciliary artery. The mechanism of vascular smooth muscle relaxation by levobunolol does not depend on endotelium or NO production. Relaxation may be mediated by inhibition of Ca²⁺release from intracellular store site.

Keywords: pharmacology • calcium • vascular cells