Vasodilatory mechanism of levobunolol on vascular smooth muscle cells.

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Dong Y, Ishikawa H, Wu Y, Yoshitomi T

Vasodilatory mechanism of levobunolol on vascular smooth muscle cells.

Exp Eye Res. 2007 Jun;84(6):1039-46. Epub 2007 Jan 27.

PubMed ID
17459374 [View in PubMed
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Abstract

Topical application of levobunolol hydrochloride, a beta-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 ([Ca(2+)](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, 1microM histamine, 10microM phenylephrine, or 100nM endothelin-1. The relaxation induced by levobunolol was concentration-dependent over the range of 10microM 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 H(1) antagonist pyrilamine. Radioligand binding experiments showed that levobunolol did not bind to the H(1) receptor. Further, histamine induced transient contraction in Ca(2+)-free solution, and levobunolol inhibited this contraction by 74.6+/-11.0%. In cultured smooth muscle cells in the presence of extracellular Ca(2+), levobunolol significantly inhibited the histamine-induced elevation of [Ca(2+)](i). However, it did not inhibit the increase of [Ca(2+)](i) in histamine-stimulated cells incubated in Ca(2+)-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 Ca(2+) entry through non-voltage-dependent Ca(2+) channels. Second, levobunolol may change the Ca(2+) sensitivity of vascular smooth muscle cells.

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