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Study of the mechanisms involved in the vasorelaxation induced by (−)-epigallocatechin-3-gallate in rat aorta
class="enumerated" style="list-style-type:decimal">This study investigated several mechanisms involved in the vasorelaxant effects of (−)-epigallocatechin-3-gallate (EGCG).EGCG (1 μM–1 mM) concentration dependently relaxed, after a transient increase in tension, contractions induced by noradrenaline (NA, 1 μM), high extracellular KCl (60 mM), or phorbol 12-myristate 13-acetate (PMA, 1 μM) in intact rat aortic rings. In a Ca2+-free solution, EGCG (1 μM–1 mM) relaxed 1 μM PMA-induced contractions, without previous transient contraction. However, EGCG (1 μM–1 mM) did not affect the 1 μM okadaic acid-induced contractions. Removal of endothelium and/or pretreatment with glibenclamide (10 μM), tetraethylammonium (2 mM) or charybdotoxin (100 nM) plus apamin (500 nM) did not modify the vasorelaxant effects of EGCG. In addition, EGCG noncompetitively antagonized the contractions induced by NA (in 1.5 mM Ca2+-containing solution) and Ca2+ (in depolarizing Ca2+-free high KCl 60 m class="small-caps">M solution).In rat aortic smooth muscle cells (RASMC), EGCG (100 μ class="small-caps">M) reduced increases in cytosolic free Ca2+ concentration ([Ca2+]i) induced by angiotensin II (ANG II, 100 n class="small-caps">M) and KCl (60 m class="small-caps">M) in 1.5 m class="small-caps">M CaCl2-containing solution and by ANG II (100 n class="small-caps">M) in the absence of extracellular Ca2+.In RASMC, EGCG (100 μ class="small-caps">M) did not modify basal generation of cAMP or cGMP, but significantly reversed the inhibitory effects of NA (1 μ class="small-caps">M) and high KCl (60 m class="small-caps">M) on cAMP and cGMP production.EGCG inhibited the enzymatic activity of all the cyclic nucleotide PDE isoenzymes present in vascular tissue, being more effective on PDE2 (IC50∼17) and on PDE1 (IC50∼25).Our results suggest that the vasorelaxant effects of EGCG in rat aorta are mediated, at least in part, by an inhibition of PDE activity, and the subsequent increase in cyclic nucleotide levels in RASMC, which, in turn, can reduce agonist- or high KCl concentration-induced increases in [Ca2+]i.
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机译：class =“ enumerated” style =“ list-style-type：decimal”> <！-list-behavior =枚举前缀-word = mark-type = decimal max-label-size = 0-> 这项研究调查了（-）-表没食子儿茶素-3-没食子酸酯（EGCG）血管舒张作用的几种机制。 EGCG（1 μM–1 mM）的浓度在张力暂时升高后依存地放松，去甲肾上腺素（NA，1μM），高细胞外KCl（60 mM）或佛波醇12-肉豆蔻酸13-乙酸盐（PMA，1μM）引起的收缩。在不含Ca 2 + 的溶液中，EGCG（1 μM–1 mM）放松了1μMPMA引起的收缩，而没有先前的短暂收缩。但是，EGCG（1 μM–1 mM）并没有影响1μM冈田酸引起的收缩。去除内皮和/或用格列本脲（10μm），四乙铵（2μmM）或炭疽毒素（100μnM）加木瓜蛋白酶（500μnM）预处理不会改变EGCG的血管舒张作用。此外，EGCG非竞争性拮抗NA（在含1.5μmMCa 2 + 的溶液中）和Ca 2 + （在去极化Ca 2+ < / sup> -free高KCl 60 m class =“ small-caps”> M 溶液）。 在大鼠主动脉平滑肌细胞（RASMC）中，EGCG（100（μ class =“ small-caps”> M ）减少了血管紧张素II（[Ca 2 + ] i）诱导的胞浆游离Ca 2 + i浓度增加（ ANG II，1.5 m class =“ 100 n class =” small-caps“> M ）和KCl（60 m class =” small-caps“> M ）在1.5 m class =” small-caps> M CaCl2溶液和ANG II（100 n class =“ small-caps”> M ）在细胞外Ca 2+不存在的情况下。 在RASMC中，EGCG（100μm class =“ small-caps”> M ）不会改变cAMP或cGMP的基础生成，但会显着逆转cAMP或cGMP的抑制作用。在cAMP和cGMP p上不适用（1μ class =“ small-caps”> M ）和高KCl（60 m class =“ small-caps”> M ） EGCG抑制血管组织中所有环状核苷酸PDE同工酶的酶活性，对PDE2（IC50〜17）和PDE1（IC50〜25）更有效。 < li>我们的研究结果表明，EGCG在大鼠主动脉中的血管舒张作用至少部分是通过抑制PDE活性以及随后RASMC中环核苷酸水平的升高而介导的，这反过来又可以降低激动剂或KCl浓度高引起的[Ca 2 + ] i增加。
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