Green tea catechins evoke a phasic contraction in rat aorta via H2O2-mediated multiple-signalling pathways.
1. The contractile effects of tea polyphenols (TP) and its four principle catechins, namely (-)-epicatechin (EC), (-)-epicatechin-3-gallate (ECG), (-)-epigallocatechin (EGC) and (-)-epigallocatechin-3-gallate (EGCG), on rat aorta contractility were investigated using the isometric tension recording technique. 2. At concentrations of 5-100 mg/L, TP evoked phasic contraction of rat aorta in a concentration-dependent but endothelium-independent manner. Of the four catechins tested, EGCG and EGC (3-300 micromol/L), but not EC and ECG, mimicked the contractile response to TP, suggesting that the epigallol moiety in the B ring may be associated with the contractile effect. 3. Contractions in response to EGCG and EGC were not affected by several endogenous vasoconstrictor receptor antagonists, but could be abolished by 10 micro mol/L BAPTA-AM, a membrane-permeable Ca2+ chelator, or attenuated by removal of extracellular Ca2+, suggesting the involvement of both intracellular and extracellular Ca2+ in evoking the contraction. 4. Pretreatment with non-selective Ca2+ channel antagonists mefenamic acid (10 micro mol/L), tetrandrine (30 micro mol/L) and SKF 96365 (30 micromol/L), but not nifedipine (1 micromol/L), the selective inhibitor of voltage-dependent Ca2+ channels, inhibited the contractile responses to EGC and EGCG, indicating the involvement of Ca2+ influx via non-voltage dependent Ca2+ channels. 5. Several intracellular Ca2+ channel modulators, including procaine (5 mmol/L), dantrolene (30 micromol/L) and 2-amino ethoxydiphenyl borate (50 micromol/L; an inositol 1,4,5-trisphosphate receptor inhibitor), also inhibited EGCG- and EGC-induced contractions, thus suggesting a role of intracellular Ca2+ release in these contractions. 6. Both EGCG- and EGC-induced contractions were depressed, to different degrees, by inhibitors of several receptor-coupled enzymes, including phospholipase C, protein kinase C, phospholipase A2 and tyrosine kinase. Furthermore, both EGCG- and EGC-induced contractions were completely abolished by catalase, but not by superoxide dismutase or mannitol/dimethyl sulphoxide. 7. Taken together, these data show, for the first time, that TP and its related catechins that contain an epigallol structure in the B ring, as in EGCG and EGC, exert direct contractile effects on rat aortic smooth muscle via a H2O2-mediated pathway.
Shen
Jian-Zhong
JZ
Department of Pharmacology, School of Medicine, Zhejiang University, Hubin Campus, Hangzhou, People's Republic of China.
Zheng
Xiu-Feng
XF
Wei
Er-Qing
EQ
Kwan
Chiu-Yin
CY
D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D002392:Catechin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008297:Male; D015394:Molecular Structure; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013662:Tea / Q000737:chemistry*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D013662:Tea; D002392:Catechin; D006861:Hydrogen Peroxide; D002118:Calcium