(+/−)‐Naringenin as large conductance Ca²⁺‐activated K⁺ (BK_Ca) channel opener in vascular smooth muscle cells

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 patch‐clamp experiments, respectively. Key results. (+/−)‐Naringenin induced concentration‐dependent relaxation in endothelium‐denuded rat aortic rings pre‐contracted with either 20 mM KCl or noradrenaline (pIC50 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‐β‐neohesperidoside] caused a concentration‐dependent 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. British Journal of Pharmacology (2006) 149, 1013–1021. doi:

Effects of adlay hull extracts on uterine contraction and Ca2+mobilization in the rat

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Naringenin attenuates pressure overload-induced cardiac hypertrophy

“…The dietary consumption of citrus fruits is associated with a reduced rate of acute coronary events (7), and naringenin appears to exert beneficial effects on the cardiovascular system (8). Naringenin has been demonstrated to promote endothelium-independent vasorelaxing effects on rat aortic rings that have been precontracted with noradrenaline (9). Furthermore, naringenin may be able to alleviate myocardial ischemia/reperfusion injury (10).…”

Urinary Bladder-Relaxant Effect of Kurarinone Depending on Potentiation of Large-Conductance Ca2+-Activated K+ Channels

“…These results provide important information about the structure-activity relationship of various natural flavanones in potentiating BK Ca channels, and guide future studies for identifying and modifying flavanone compounds. As suggested by a previous study (Saponara et al, 2006), it is encouraging to find that naringenin, a predominant flavanone in grapefruit, shows an appreciable potentiation of BK Ca channel activity because the beneficial effects of this compound are well recognized as an antioxidant, a free radical scavenger, and an immune modulator Du et al, 2009;Cavia-Saiz et al, 2010;Yilma et al, 2013).…”