Epigallocatechin-3-gallate relaxes the isolated bovine ophthalmic artery: involvement of phosphoinositide 3-kinase-Akt-nitric oxide/cGMP signalling pathway.
نویسندگان
چکیده
The present study investigates the direct action and the underlying mechanism(s) of epigallocatechin-3-gallate (EGCG) vasomotor effects on the bovine isolated ophthalmic artery. Adjacent rings were cut from each artery and mounted in a wire miograph system for isometric recording. Concentration-response curves for EGCG were constructed by adding cumulative concentrations of the drug to arterial rings pre-contracted with 5-HT (1 microM). Effects of mechanical endothelial cell removal and of selective blockers of the nitric oxide (NO)/cGMP pathways were investigated on the EGCG relaxant responses. EGCG relaxed ophthalmic arteries and maximum relaxation was 78.4+/-2.64%. Mechanical removal of endothelium, blockade of soluble guanylyl cyclase by 1H-1,2,4-oxadiazolo [4,3-a]quinoxalin-1-one (ODQ, 1 and 5 microM) or inhibition of nitric oxide (NO) synthase by N(G)-nitro-L-arginine (L-NAME, 50 and 100 microM) reduced significantly the relaxant response to catechin; moreover, the NO donor S-nitroso-N-acetylpenicillamine (SNAP, 100 microM) significantly increased the vasorelaxant responses to EGCG. Relaxation to EGCG was inhibited by iberiotoxin (200 nM), a blocker of big-conductance Ca(2+)-activated K(+) (BK(Ca)) channel, whereas the blockade of K(ATP) channel by glibenclamide (5 microM) and of small-conductance Ca(2+)-activated K(+) (SK(Ca)) channel by apamin (100 nM) elicited no effect. Interestingly, also inhibition of phosphoinositide-3-kinase (PI3K) by wortmannin (100 nM) and of Akt by SH6 (1 microM) markedly decreased the EGCG-evoked vasorelaxation. These data suggest that EGCG induced vasorelaxation in ophthalmic arteries with endothelium-intact via the activation of the NO/cGMP signalling pathway and defined an intriguing role for PI3K and Akt as upstream mediators for activation of NO-mediated relaxant responses.
منابع مشابه
A Constituent of Green Tea, Epigallocatechin-3-gallate, Activates Endothelial Nitric Oxide Synthase by a PI3K-, PKA-, and Akt-dependent Pathway, and Leads to Endothelial-dependent Vasorelaxation
متن کامل
Valsartan regulates the interaction of angiotensin II type 1 receptor and endothelial nitric oxide synthase via Src/PI3K/Akt signalling.
AIMS Valsartan, a selective angiotensin II type 1 receptor (AT1R) blocker, has beneficial effects in the cardiovascular system in part by its increase of nitric oxide (NO) bioavailability, yet the mechanisms are unclear. We investigated the molecular mechanisms underlying this effect in endothelial cells (ECs). METHODS AND RESULTS NO production was examined by Griess reagent assay, DAF-2 DA f...
متن کاملEstrogen receptor activation of phosphoinositide-3 kinase, akt, and nitric oxide signaling in cerebral blood vessels: rapid and long-term effects.
Estrogen receptor regulation of nitric oxide production by vascular endothelium may involve rapid, membrane-initiated signaling pathways in addition to classic genomic mechanisms. In this study, we demonstrate using intact cerebral blood vessels that 17beta-estradiol rapidly activates endothelial nitric-oxide synthase (eNOS) via a phosphoinositide-3 (PI-3) kinase-dependent pathway. The effect i...
متن کاملMechanism of endothelial nitric oxide synthase phosphorylation and activation by thrombin.
Thrombin has been shown to activate endothelial NO synthase (eNOS) leading to endothelium-dependent vasorelaxation. In addition to its activation by Ca2+/calmodulin, eNOS has several regulatory sites. Ser1179 phosphorylation of eNOS by the phosphatidylinositol 3-kinase-dependent Akt stimulates its catalytic activity. In this study, we have elucidated the signaling mechanism of thrombin-induced ...
متن کاملInhibition of phosphoinositide 3-kinase potentiates relaxation of porcine coronary arteries induced by nitroglycerin by decreasing phosphodiesterase type 5 activity.
BACKGROUND Vessel tension can be modulated by phosphoinositide 3-kinase (PI3K) acting on l-type calcium channel, rho kinase and phosphodiesterase (PDE) type 3 in smooth muscle cells. Inhibition of PI3K could increase the relaxation of porcine coronary arteries to nitroglycerin independent of this pathway, and the aim of the present study was therefore to determine the underlying mechanisms. M...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- European journal of pharmacology
دوره 608 1-3 شماره
صفحات -
تاریخ انتشار 2009