Vascular relaxation by ethanol extract of Xanthoceras sorbifolia via Akt- and SOCE-eNOS-cGMP pathways.
OBJECTIVE
The aim of the present study was to define the effect of Xanthoceras sorbifolia extracts (XS) on vascular tension and responsible mechanisms in rat thoracic aortic rings.


METHODS
Ethanol extract of the leaves of XS (EXS) was examined for their vascular relaxant effects in isolated phenylephrine-precontracted rat thoracic aorta.


RESULTS
EXS (0.1-100 μg/ml) induced relaxation of the phenylephrine-precontracted aortic rings in a concentration-dependent manner. Endothelium-denudation abolished EXS-induced vasorelaxation. Pretreatment of the endothelium-intact aortic rings with N(G)-nitro-L-arginine methylester (L-NAME) and 1H-[1,2,4]-oxadiazolo-[4,3-α]-quinoxalin-1-one (ODQ) inhibited EXS-induced vasorelaxation. Inhibition of Ca(2+) entry via L-type Ca(2+) channels failed to block the EXS-induced vasorelaxation. Extracellular Ca(2+) depletion significantly attenuated EXS-induced vasorelaxation. Modulators of the store-operated Ca(2+) entry (SOCE), thapsigargin, 2-aminoethyl diphenylborinate (2-APB) and Gd(3+), and an inhibitor of Akt, wortmannin, markedly attenuated the EXS-induced vasorelaxation. EXS increased cGMP levels of the aortic rings in a concentration-dependent manner and the effect was blocked by L-NAME, ODQ, thapsigargin, Gd(3+), 2-APB, and wortmannin. Further, EXS-induced vasorelaxation was significantly attenuated by tetraethylammonium, a non-selective K(ca) channels blocker, but not by glibenclamide, an ATP-sensitive K(+) channels inhibitor. Inhibition of cyclooxygenase with indomethacin, and adrenergic and muscarinic receptors blockade had no effects on EXS-induced vasorelaxation.


CONCLUSIONS
The present study suggests that EXS relaxes vascular smooth muscle via endothelium-dependent NO-cGMP signaling through activation of the Akt- and SOCE-eNOS-sGC pathways, which may, at least in part, be related to the function of K(+) channels.
Jin
Song Nan
SN
Institute of Materia Medica, Taishan Medical University, Middle of Changcheng Road, Taian, Shandong 271016, China. snjin0504@yahoo.com.cn
Wen
Jin Fu
JF
Kim
Hye Yoom
HY
Kang
Dae Gill
DG
Lee
Ho Sub
HS
Cho
Kyung Woo
KW
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000201:enzymology; D002118:Calcium / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D004365:Drugs, Chinese Herbal / Q000302:isolation & purification / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D000431:Ethanol; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D018515:Plant Leaves / Q000737:chemistry; D015221:Potassium Channels / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D029631:Sapindaceae / Q000737:chemistry*; D015398:Signal Transduction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000302:isolation & purification / Q000494:pharmacology*
D004365:Drugs, Chinese Herbal; D015221:Potassium Channels; D014665:Vasodilator Agents; D009569:Nitric Oxide; D000431:Ethanol; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D051057:Proto-Oncogene Proteins c-akt; D006152:Cyclic GMP; D002118:Calcium