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 7 microM methoxamine, perfusion of ELE (107102 mg/ml for 15 min) 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 NG-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 18alpha-glycyrrhetinic acid (18alpha-GA, a gap-junction inhibitor), and abolished by high K-containing Krebs' 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.
Jin
Xin
X
Department of Clinical Pharmaceutical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.
Otonashi-Satoh
Yukiko
Y
Sun
Pengyuan
P
Kawamura
Naomi
N
Tsuboi
Takashi
T
Yamaguchi
Yasuyo
Y
Ueda
Taro
T
Kawasaki
Hiromu
H
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001685:Biological Factors / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D031283:Eucommiaceae; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D018515:Plant Leaves; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014655:Vascular Resistance / Q000187:drug effects* / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
D001685:Biological Factors; D004365:Drugs, Chinese Herbal; D004791:Enzyme Inhibitors; D026902:Potassium Channel Blockers; D014665:Vasodilator Agents; C067410:endothelium-dependent hyperpolarization factor; D001285:Atropine; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin