Large Conductance Ca²⁺-Activated K⁺ (BK_Ca) Channels are Involved in the Vascular Relaxations Elicited by Piceatannol Isolated from Rheum undulatum rhizome

Abstract

We previously reported that piceatannol isolated from the rhizome extract of Rheum undulatum has a potent vasorelaxant activity. In the present study, the mechanisms underlying the direct vascular relaxant effect of piceatannol were investigated in isolated rat aorta. Piceatannol induced a concentration-dependent relaxation in aortic preparations precontracted with phenylephrine (EC₅₀ : 2.4 ± 0.4 μM), which was completely inhibited by endothelial removal, N _ω-nitro-L-arginine (nitric oxide synthase inhibitor), methylene blue and 1H-[1] [2] [4]oxadiazolo [4,3-a]quinoxalin-1-one (guanylyl cyclase inhibitor). The piceatannol-induced relaxation was also blocked by raising the extracellular K⁺ (45 mM), 4-aminopyridine (voltage-sensitive K⁺ channel blocker) and tetraethylammonium [the non-selective Ca²⁺-activated K⁺ (K_Ca) channel blocker] but not by indomethacin (cyclooxygenase inhibitor), atropine (muscarinic receptor antagonist), propranolol (β-adrenoceptor antagonist), verapamil and nifedipine (L-type voltage-gated Ca²⁺ channel blocker), barium chloride (inward rectifier K⁺ channel inhibitor) and glibenclamide (ATP-sensitive K⁺ channel blocker). In further studies investigating the role of Ca²⁺-activated K⁺ (K_Ca) channels, piceatannol-induced relaxant responses were decreased by charybdotoxin [large (BK_Ca)- and intermediate (IK_Ca)-conductance K_Ca channel blocker], iberiotoxin (selective BK_Ca channels blocker), but not by apamin [small-conductance K_Ca (SK_Ca) channel blocker], TRAM-34 [intermediate-conductance K_Ca (IK_Ca) channel blocker]. The present results demonstrate that piceatannol-induced vascular relaxation in rat aorta may be mediated by an endothelium-dependent nitric oxide signaling pathway, at least partially, through the activation of BK_Ca.

Abbreviations

BK_Ca channel: large conductance K_Ca channel

IK_Ca channel: intermediate conductance K_Ca channel

K_ATP channel: ATP-sensitive K⁺ channel

K_Ca channel: Ca²⁺-activated K⁺ channel

K_IR channel: inward rectifier K⁺ channel

Kv channel: voltage-dependent K⁺ channel

L-NNA: N _ω-nitro-L-arginine

MB: methylene blue

ODQ: 1H-[1] [2] [4] oxadiazolo[4,3-a]quinoxalin-1-one

SK_Ca channel: small conductance K_Ca channel

TEA: tetraethylammonium

TRAM 34: 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole

Key words

Rheum undulatum - Polygonaceae - piceatannol - vasorelaxation - Ca²⁺-activated K⁺ channel - BK_Ca channels - rat aorta

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