Endothelial NO/cGMP-Dependent Vascular Relaxation of Cornuside Isolated from the Fruit of Cornus officinalis

Abstract

Cornuside is a bisiridoid glucoside compound isolated from the fruit of Cornus officinalis Sieb. et Zucc. (Cornaceae). In the present study, we investigated the effect of cornuside on vascular tone in rat aortic tissue. Cornuside induced a concentration-dependent relaxation of the phenylephrine-precontracted rat aorta, which was abolished by removal of the endothelial layer. Pretreatment of the aortic tissues with either N ^G-nitro-L-arginine methyl ester (L-NAME) or 1H-[1] [2] [4]-oxadiazole-[4,3-α]-quinoxalin-1-one (ODQ) completely inhibited the relaxation induced by cornuside. However, the relaxant effect of cornuside was not blocked by pretreatment with verapamil, diltiazem, tetraethylammonium (TEA), glibenclamide, indomethacin, atropine, or propranolol. In addition, incubation of human umbilical vein endothelial cells (HUVECs) with cornuside increased the production of cGMP in a dose-dependent manner, but this effect was blocked by pretreatment with L-NAME and ODQ, respectively. Taken together, the present study suggests that cornuside dilates vascular smooth muscle via endothelium-dependent nitric oxide (NO)/cGMP signaling.

Abbreviations

ATP:adenosine triphosphate

cGMP:guanosine 3′,5′-cyclic monophosphate

DMSO:dimethyl sulfoxide

EDHF:endothelium-derived hyperpolarizing factor

EDRF:endothelium-derived relaxing factor

EDTA:ethylenediaminetetraacetic acid

FBS:fetal bovine serum

HUVECs:human umbilical vein endothelial cells

IBMX:3-isobutyl-1-methylxanthine

L-NAME:N ^G-nitro-L-arginine methyl ester

NO:nitric oxide

ODQ:1H-[1] [2] [4]-oxadiazole-[4,3-α]-quinoxalin-1-one

RIA:radioimmunoassay

TEA: tetraethylammonium

Key words

Cornus officinalis - Cornaceae - cornuside - vasorelaxation - nitric oxide/cGMP

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