Enhancement of contraction of rat mesenteric artery by acteoside: role of endothelial nitric oxide.

Abstract

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.