Large conductance Ca2+-activated K+ (BKCa) channels are involved in the vascular relaxations elicited by piceatannol isolated from Rheum undulatum rhizome.
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 (EC (50) : 2.4 +/- 0.4 microM), which was completely inhibited by endothelial removal, N(omega)-nitro- L-arginine (nitric oxide synthase inhibitor), methylene blue and 1 H- 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 Ca (2+)-activated K (+) (K (Ca)) channel blocker] but not by indomethacin (cyclooxygenase inhibitor), atropine (muscarinic receptor antagonist), propranolol (beta-adrenoceptor antagonist), verapamil and nifedipine (L-type voltage-gated Ca (2+) channel blocker), barium chloride (inward rectifier K (+) channel inhibitor) and glibenclamide (ATP-sensitive K (+) channel blocker). In further studies investigating the role of Ca (2+)-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).
Oh
Kwang-Seok
KS
Drug Discovery Division, Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea.
Ryu
Shi Yong
SY
Kim
Young Sup
YS
Lee
Byung Ho
BH
D000818:Animals; D001011:Aorta / Q000187:drug effects; D004553:Electric Conductivity; D015394:Molecular Structure; D024681:Potassium Channels, Calcium-Activated / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012250:Rheum / Q000737:chemistry*; D027343:Rhizome / Q000737:chemistry*; D013267:Stilbenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*
D024681:Potassium Channels, Calcium-Activated; D013267:Stilbenes; C041525:3,3',4,5'-tetrahydroxystilbene