Enhancement of contraction of rat mesenteric artery by acteoside: role of endothelial nitric oxide.
The present study describes the role of endothelium in the vascular response to purified acteoside from Ligustrum purpurascens in rat mesenteric arteries. In endothelium-intact rings, acteoside (3-50 micromol/L) enhanced phenylephrine-induced contraction without affecting the maximum response. This enhancement was absent in endothelium-denuded rings. Pretreatment with nitric oxide synthase (NOS) inhibitors, N(G)-nitro-L-arginine (L-NNA, 100 micromol/L) and N(G)-nitro-L-arginine methyl ester (L-NAME, 100 micromol/L), or a selective guanylyl cyclase inhibitor, 1H-[1,2,4]oxadiazolo[4,2-alpha]quinoxalin-1-one (ODQ, 10 micromol/L), increased both the sensitivity of vasoconstriction to phenylephrine and the maximal response. The enhancing effect of acteoside (30 micromol/L) was abolished in the presence of L-NAME, L-NNA, or ODQ. Tetraethylammonium (TEA(+), 3 mmol/L), a putative K(+) channel blocker, also abolished the effect of acteoside. CaCl2 (0.01-10 mmol/L) induced contractions in 50 mmol/L K(+)-containing Krebs solution. Neither acteoside nor TEA(+) affected CaCl2-induced contraction in elevated K(+) solution. Acteoside (30 micromol/L) attenuated acetylcholine-induced endothelium-dependent relaxation. Acteoside did not influence relaxation induced by exogenous NO donors, hydroxylamine or sodium nitroprusside, in endothelium-denuded rings. Acteoside did not alter endothelium-independent relaxation induced by forskolin or NS 1619. The present results indicate that acteoside enhanced the evoked vasoconstriction, mainly through inhibition of endothelial NO production/release and inhibition of NO-mediated TEA(+)-sensitive activation of K(+) channels.
Tam
Wing-Yin
WY
Department of Physiology, Chinese University of Hong Kong, Hong Kong, China.
Chen
Zhen-Yu
ZY
He
Zhen-Dan
ZD
Yao
Xiaoqiang
X
Lau
Chi-Wai
CW
Huang
Yu
Y
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005960:Glucosides / Q000494:pharmacology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects*; D015394:Molecular Structure; D009119:Muscle Contraction / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010636:Phenols / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology; D010946:Plants, Medicinal / Q000737:chemistry*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects; D059808:Polyphenols
D000109:Acetylcholine; D001562:Benzimidazoles; D004791:Enzyme Inhibitors; D005960:Glucosides; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D009599:Nitroprusside; D010636:Phenols; D010656:Phenylephrine; D015221:Potassium Channels; C086491:NS 1619; C058956:acteoside; D059808:Polyphenols