Endothelium-derived Hyperpolarizing Factor (EDHF) Mediates Endothelium-dependent Vasodilator Effects of Aqueous Extracts from Eucommia ulmoides Oliv. Leaves in Rat Mesenteric Resistance Arteries

The vascular effects of an aqueous extract prepared from the leaves of Eucommia ulmoides Oliv. (ELE), a medicinal herb commonly used in antihypertensive herbal prescriptions in China, were investigated in rat mesenteric resistance arteries. The mesenteric vascular bed was perfused with Krebs solution and the perfusion pressure was measured with a pressure transducer. In preparations with an intact endothelium and precontracted with 7μM methoxamine, perfusion of ELE (10^－7－10^－2mg/ml for 15min) caused a concentration-dependent vasodilatation, which was abolished by chemical removal of the endothelium. The ELE-induced vasodilatation was inhibited by neither indomethacin (INDO, a cyclooxygenase inhibitor) nor N^G-nitro-L-arginine-methyl ester (L-NAME, a nitric oxide inhibitor). The ELE-induced vasodilatation was significantly inhibited by tetraethylammonium (TEA, a K⁺ channel blocker) and 18α-glycyrrhetinic acid (18α-GA, a gap-junction inhibitor), and abolished by high K⁺ -containing Krebsʼ solution. Atropine (a muscarinic acetylcholine receptor antagonist) significantly inhibited the vasodilatation induced by ELE at high concentrations. These results suggest that the ELE-induced vasodilatation is endothelium-dependent but nitric oxide (NO)- and prostaglandin I₂ (PGI₂)-independent, and is mainly mediated by the endothelium-derived hyperpolarizing factor (EDHF) in the mesenteric resistance arteries. Furthermore, the ELE-induced EDHF-mediated response involves the activation of K⁺-channels and gap junctions.