Vasorelaxant action of an ethylacetate fraction of Euphorbia humifusa involves NO-cGMP pathway and potassium channels.

BACKGROUND

Euphorbia humifusa Willd. (EH) is an important traditional Chinese medicine that has commonly been used for treating bacillary dysentery and enteritis in many Asian countries for thousands of years. EH has a wide variety of pharmacological actions such as antioxidant, hypotensive, and hypolipidemic effects. However, the mechanisms involved are to be defined.

OBJECTIVE

The present study was performed to evaluate the cardiovascular effects of EH in rats.

METHODS

Methanol extract of EH (MEH) and ethylacetate fraction of the MEH (EEH) was examined for their vascular relaxant effects in phenylephrine-precontracted aortic rings. Effects of EEH on systolic blood pressure and heart rate were tested in Sprague-Dawley rats.

RESULTS

MEH and EEH induced vasorelaxation in a concentration-dependent manner. Endothelium-denudation abolished the EEH-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) significantly inhibited the EEH-induced vasorelaxation. EEH increased cGMP levels of the aortic rings in a concentration-dependent manner and the effect was blocked by L-NAME or ODQ. Extracellular Ca(2+) depletion and treatments with thapsigargin, Gd(3+), and 2-aminoethyl diphenylborinate significantly attenuated the EEH-induced vasorelaxation. Wortmannin markedly attenuated the EEH-induced vasorelaxation. In addition, tetraethylammonium, iberiotoxin, and charybdotoxin, but not apamin, attenuated the EEH-induced vasorelaxation. Glibenclamide, indomethacin, atropine, and propranolol had no effects on the EEH-induced vasorelaxation. Furthermore, EEH decreased systolic blood pressure and heart rate in a concentration-dependent manner in rats.

CONCLUSIONS

The present study demonstrates that EEH induces endothelium-dependent vasorelaxation via eNOS-NO-cGMP signaling through the modification of intracellular Ca(2+), Ca(2+) entry, and large- and intermediate-conductance KCa channel homeostasis. The data also suggest that the Akt-eNOS pathway is involved in the EEH-induced vasorelaxation. EEH induces hypotension and bradycardia in vivo.