Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Original Paper Pharmacology 2008;81:110–117 DOI: 10.1159/000110011 Nebivolol Induces a Hyperpolarizing Effect on Smooth Muscle Cells in the Mouse Renal Artery by Activation of Beta-2-Adrenoceptors A. Georgescu a F. Pluteanu a M.-L. Flonta a E. Badila b M. Dorobantu b D. Popov a a University of Bucharest, Faculty of Biology, and b Emergency Hospital Bucharest, Institute of Cellular Biology and Pathology ‘N. Simionescu’, Bucharest, Romania denuded renal arteries. The results of this study show that nebivolol exerts vasodilator effects on the SMC in the de- nuded renal arteries and the maximal response is achieved at a concentration of 50 mol/l. Nebivolol effects involve binding to the  2 -adrenoceptors and the subsequent activa- tion of Ca 2+ -activated K + channels in SMC, with no contribu- tion of NO. Taken together, the study brings new insights into the mechanism underlying the nebivolol-induced arte- rial vasodilation. Copyright © 2008 S. Karger AG, Basel Introduction In physiological conditions, the renal artery plays a very important role in the control of the blood pressure [1]. In pathological conditions such as hypertension and diabetes (rats), vasodilation of the renal microcirculation is impaired [2]. In these cases, cardiovascular drugs may have beneficial effects, and these could be manifested at the level of endothelium and vascular smooth muscle cells. Nebivolol, a new selective  1 -adrenoceptor-block- ing agent with vasodilator properties, was suggested as beneficial in hypertension [3, 4] . The D-enantiomer has the  1 -blocking properties, whereas the L-enantiomer in- duces vasodilatation via  2 -adrenoceptor binding, with a Key Words Renal artery  Nebivolol  Vasodilation  Hyperpolarization Abstract Nebivolol is a highly selective  1 -adrenoceptor antagonist with vasodilator properties involving the vascular endothe- lium, but its effect on the smooth muscle cells (SMC) is still unclear. In this paper, we tested the effect of nebivolol on renal artery smooth muscle cells and investigated the cellu- lar mechanism involved. To this purpose, the denuded renal arteries isolated from mice were studied in vitro using the myograph and the nitric oxide (NO) sensor techniques, while the SMC in culture were analyzed by the patch-clamp tech- nique. The myograph technique was used to assay the vaso- dilator effect of nebivolol on the arterial muscular layer, and to establish the optimal dose of the drug to be tested on single SMC by the patch-clamp technique. Using both the myograph and the patch-clamp techniques, we examined the potential contribution of  2 -adrenoceptors and Ca 2+ -ac- tivated K + channels to the nebivolol-induced effects, by ex- posing the denuded arteries and SMC cultures to specific inhibitors such as butoxamine (100 mol/l), tetraethylam- monium (TEA, 1 mmol/l), and iberiotoxin (100 nmol/l). The direct measurement of NO using the NO sensor enabled us to evaluate if nebivolol induces/or not the release of NO in Received: June 12, 2007 Accepted: June 12, 2007 Published online: October 19, 2007 Adriana Georgescu, PhD Institute of Cellular Biology and Pathology ‘Nicolae Simionescu’ 8, BP Hasdeu Street, PO Box 35-14 RO–050568 Bucharest (Romania) Tel. +40 1 319 4518, Fax +40 1 319 4519, E-Mail adriana.georgescu@ icbp.ro © 2008 S. Karger AG, Basel 0031–7012/08/0812–0110$24.50/0 Accessible online at: www.karger.com/pha