Echinacoside elicits endothelium-dependent relaxation in rat aortic rings via an NO-cGMP pathway.
The aim of this study was to identify and elucidate the vasorelaxant activity of echinacoside, a phenylethanoid glycoside isolated from the medicinal herb Cistanche tubulosa, and its possible underlying mechanism on isolated rat thoracic aortic rings pre-contracted with phenylephrine (PE, 1 microM) and KCl (60 mM). Echinacoside (30-300 microM) exhibited an acute relaxation in endothelium-intact rings in a concentration-dependent manner, while this relaxation was significantly inhibited in endothelium-denuded condition and in the presence of the endothelial nitric oxide synthase (eNOS) inhibitor, N(W)-nitro-L-arginine methyl ester (L-NNA, 100 microM), an unselective soluble guanylate cyclase blocker, methylene blue (10 microM), the selective sGC inhibitor 1 H-[1, 2, 4]oxadiazolo[4,3- A]quinoxalin-1-one (ODQ, 1 microM); in addition, atropine (1 microM), a selective muscarinic receptor antagonist, partially affected the relaxation. However, the cyclooxygenase inhibitor indomethacin (5 microM) had no influence on the action. Echinacoside enhanced the cyclic guanosine monophosphate (cGMP) production in aortic rings contracted with PE. These results indicate for the first time that echinacoside mediates the endothelium-dependent vasodilator action in rat thoracic aortic rings through nitric oxide (NO)-cGMP pathway.
He
Wen-Jun
WJ
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing, PR China.
Fang
Tai-Hui
TH
Ma
Xu
X
Zhang
Ke
K
Ma
Zhi-Zhong
ZZ
Tu
Peng-Fei
PF
D000818:Animals; D001013:Aorta, Thoracic; D001285:Atropine / Q000494:pharmacology; D031671:Cistanche / Q000737:chemistry*; D006152:Cyclic GMP / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006027:Glycosides / Q000302:isolation & purification / Q000494:pharmacology*; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009569:Nitric Oxide / Q000378:metabolism; D010656:Phenylephrine; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D018547:Plant Stems; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D014665:Vasodilator Agents / Q000302:isolation & purification / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D006027:Glycosides; D010936:Plant Extracts; D011976:Receptors, Muscarinic; D014665:Vasodilator Agents; D010656:Phenylephrine; D009569:Nitric Oxide; D001285:Atropine; D006162:Guanylate Cyclase; D006152:Cyclic GMP; C060297:echinacoside