Ethanol extract of the leaves of XS (EXS) was examined for their vascular relaxant effects in isolated phenylephrine-precontracted rat thoracic aorta.
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 NG-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 Ca2+ entry via l-type Ca2+ channels failed to block the EXS-induced vasorelaxation. Extracellular Ca2+ depletion significantly attenuated EXS-induced vasorelaxation. Modulators of the store-operated Ca2+ entry (SOCE), thapsigargin, 2-aminoethyl diphenylborinate (2-APB) and Gd3+, 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, Gd3+, 2-APB, and wortmannin. Further, EXS-induced vasorelaxation was significantly attenuated by tetraethylammonium, a non-selective Kca 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.
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.