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Abstract #17969 Published in IGR 9-2
Vasodilatory mechanism of levobunolol on vascular smooth muscle cells
Dong Y; Ishikawa H; Wu Y; Yoshitomi TExperimental Eye Research 2007; 84: 1039-1046
Topical application of levobunolol hydrochloride, a β-adrenergic antagonist used for treatment of glaucoma, is reported to increase ocular blood flow. We studied the mechanism of levobunolol-induced vasodilation in arterial smooth muscle. The effects of levobunolol or other agents on isolated, pre-contracted rabbit ciliary artery were investigated using an isometric tension recording method. The effects of the same agents on intracellular free calcium (Ca2+i) in cultured human aortic smooth muscle cells were also studied by fluorophotometry. Levobunolol relaxed ciliary artery rings that were pre-contracted with either high-K solution, 1μM histamine, 10μM phenylephrine, or 100nM endothelin-1. The relaxation induced by levobunolol was concentration-dependent over the range of 10μM to 0.3mM. Inhibition of endothelial nitric oxide synthase or denudation of the endothelium did not affect this relaxation. Histamine-induced contractions were inhibited by the histamine H1 antagonist pyrilamine. Radioligand binding experiments showed that levobunolol did not bind to the H1 receptor. Further, histamine induced transient contraction in Ca2+-free solution, and levobunolol inhibited this contraction by 74.6±11.0%. In cultured smooth muscle cells in the presence of extracellular Ca2+, levobunolol significantly inhibited the histamine-induced elevation of Ca2+i. However, it did not inhibit the increase of Ca2+i in histamine-stimulated cells incubated in Ca2+-free solution. These results indicate that levobunolol may relax rabbit ciliary artery by two different mechanisms. First, the relaxation could be due to the blockade of Ca2+ entry through non-voltage-dependent Ca2+ channels. Second, levobunolol may change the Ca2+ sensitivity of vascular smooth muscle cells.
Dr. Y. Dong, Department of Ophthalmology, Akita University School of Medicine, 1-1-1 Hondo, Akita, Akita 010-8543, Japan; Department of Ophthalmology, The Second Hospital of Jilin University, Jilin 130042, P.R. China
Classification:
11.3.4 Betablocker (Part of: 11 Medical treatment > 11.3 Adrenergic drugs)
6.11 Bloodflow measurements (Part of: 6 Clinical examination methods)
