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Nebivolol induces a hyperpolarizing effect on smooth muscle cells in the mouse renal artery by activation of beta-2-adrenoceptors

Domenii publicaţii > Biologie + Tipuri publicaţii > Articol în revistã ştiinţificã

Autori: A. Georgescu, F. Pluteanu, M.-L. Flonta, E. Badila, M. Dorobantu, D. Popov

Editorial: S. Karger AG, Basel, Pharmacology, 81, p.110-117, 2008.


Nebivolol is a highly selective beta 1 -adrenoceptor antagonist with vasodilator properties involving the vascular endothelium, 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 cellular 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 technique. The myograph technique was used to assay the vasodilator 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 beta 2 -adrenoceptors and Ca 2+ -activated K + channels to the nebivolol-induced effects, by exposing the denuded arteries and SMC cultures to specific inhibitors such as butoxamine (100 micro mol/l), tetraethylammonium (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 indenuded renal arteries. The results of this study show that
nebivolol exerts vasodilator effects on the SMC in the denuded renal arteries and the maximal response is achieved
at a concentration of 50 micro mol/l. Nebivolol effects involve binding to the beta 2 -adrenoceptors and the subsequent activation of Ca 2+ -activated K + channels in SMC, with no contribution of NO. Taken together, the study brings new insights into the mechanism underlying the nebivolol-induced arterial vasodilation.

Cuvinte cheie: artera renala, nebivolol, vasodilatare,hiperpolarizare // Renal artery, Nebivolol, Vasodilation, Hyperpolarization