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Vasodilatory mechanism of levobunolol on vascular smooth muscle cells
- Source :
-
Experimental Eye Research . Jun2007, Vol. 84 Issue 6, p1039-1046. 8p. - Publication Year :
- 2007
-
Abstract
- Abstract: 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. [Copyright &y& Elsevier]
- Subjects :
- *SMOOTH muscle
*MUSCLE cells
*ANTIHISTAMINES
*EYE diseases
Subjects
Details
- Language :
- English
- ISSN :
- 00144835
- Volume :
- 84
- Issue :
- 6
- Database :
- Academic Search Index
- Journal :
- Experimental Eye Research
- Publication Type :
- Academic Journal
- Accession number :
- 25182912
- Full Text :
- https://doi.org/10.1016/j.exer.2007.01.010