Background and purpose. The aim of this study was to investigate, in vascular smooth muscle cells, the mechanical and electrophysiological effects of (+/-) -naringenin. Experimental approach. Aorta ring preparations and single tail artery myocytes were employed for functional and patchclamp experiments, respectively. Key results. (+/-)- Naringenin induced concentration-dependent relaxation in endothelium-denuded rat aortic rings precontracted with either 20 mM KCl or noradrenaline (pIC(50) values of 4.74 and 4.68, respectively). Tetraethylammonium, iberiotoxin, 4-aminopyridine and 60 mM KCl antagonised (+/-)-naringenin-induced vasorelaxation, while glibenclamide did not produce any significant antagonism. Naringin [(+/-)-naringenin 7-beta-neohesperidoside] caused a concentrationdependent relaxation of rings pre-contracted with 20 mM KCl, although its potency and efficacy were significantly lower than those of (+/-)-naringenin. In rat tail artery myocytes, (+/-)-naringenin increased large conductance Ca2+-activated K+ (BKCa) currents in a concentration-dependent manner; this stimulation was iberiotoxin-sensitive and fully reversible upon drug wash-out. (+/-)-Naringenin accelerated the activation kinetics of BKCa current, shifted, by 22 mV, the voltage dependence of the activation curve to more negative potentials, and decreased the slope of activation. (+/-)-Naringenin-induced stimulation of BKCa current was insensitive either to changes in the intracellular Ca2+ concentration or to the presence, in the pipette solution, of the fast Ca2+ chelator BAPTA. However, such stimulation was diminished when the K+ gradient across the membrane was reduced. Conclusions and Implications. The vasorelaxant effect of the naturally-occurring flavonoid (+/-)-naringenin on endothelium-denuded vessels was due to the activation of BKCa channels in myocytes.

(+/-)-NARINGENIN AS LARGE CONDUCTANCE Ca2+-ACTIVATED K+ (BKCa) CHANNEL OPENER IN VASCULAR SMOOTH MUSCLE CELLS

TESTAI, LARA;MARTELLI, ALMA;CHERICONI S;CALDERONE, VINCENZO
2006

Abstract

Background and purpose. The aim of this study was to investigate, in vascular smooth muscle cells, the mechanical and electrophysiological effects of (+/-) -naringenin. Experimental approach. Aorta ring preparations and single tail artery myocytes were employed for functional and patchclamp experiments, respectively. Key results. (+/-)- Naringenin induced concentration-dependent relaxation in endothelium-denuded rat aortic rings precontracted with either 20 mM KCl or noradrenaline (pIC(50) values of 4.74 and 4.68, respectively). Tetraethylammonium, iberiotoxin, 4-aminopyridine and 60 mM KCl antagonised (+/-)-naringenin-induced vasorelaxation, while glibenclamide did not produce any significant antagonism. Naringin [(+/-)-naringenin 7-beta-neohesperidoside] caused a concentrationdependent relaxation of rings pre-contracted with 20 mM KCl, although its potency and efficacy were significantly lower than those of (+/-)-naringenin. In rat tail artery myocytes, (+/-)-naringenin increased large conductance Ca2+-activated K+ (BKCa) currents in a concentration-dependent manner; this stimulation was iberiotoxin-sensitive and fully reversible upon drug wash-out. (+/-)-Naringenin accelerated the activation kinetics of BKCa current, shifted, by 22 mV, the voltage dependence of the activation curve to more negative potentials, and decreased the slope of activation. (+/-)-Naringenin-induced stimulation of BKCa current was insensitive either to changes in the intracellular Ca2+ concentration or to the presence, in the pipette solution, of the fast Ca2+ chelator BAPTA. However, such stimulation was diminished when the K+ gradient across the membrane was reduced. Conclusions and Implications. The vasorelaxant effect of the naturally-occurring flavonoid (+/-)-naringenin on endothelium-denuded vessels was due to the activation of BKCa channels in myocytes.
Saponara, S; Testai, Lara; Iozzi, D; Martinotti, E; Martelli, Alma; Chericoni, S; Sgaragli, G; Fusi, F; Calderone, Vincenzo
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11568/181908
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