Study of the mechanisms involved in the vasorelaxation induced by (−)‐epigallocatechin‐3‐gallate in rat aorta

Abstract

1 This study investigated several mechanisms involved in the vasorelaxant effects of (À)-epigallocatechin-3-gallate (EGCG). 2 EGCG (1 mM-1 mM) concentration dependently relaxed, after a transient increase in tension, contractions induced by noradrenaline (NA, 1 mM), high extracellular KCl (60 mM), or phorbol 12-myristate 13-acetate (PMA, 1 mM) in intact rat aortic rings. In a Ca 2 þ -free solution, EGCG (1 mM-1 mM) relaxed 1 mM PMA-induced contractions, without previous transient contraction. However, EGCG (1 mM-1 mM) did not affect the 1 mM okadaic acid-induced contractions. Removal of endothelium and/or pretreatment with glibenclamide (10 mM), 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 Ca 2 þ -containing solution) and Ca 2 þ (in depolarizing Ca 2 þ -free high KCl 60 mM solution). 3 In rat aortic smooth muscle cells (RASMC), EGCG (100 mM) reduced increases in cytosolic free Ca 2 þ concentration ([Ca 2 þ ] i ) induced by angiotensin II (ANG II, 100 nM) and KCl (60 mM) in 1.5 mM CaCl 2 -containing solution and by ANG II (100 nM) in the absence of extracellular Ca 2 þ . 4 In RASMC, EGCG (100 mM) did not modify basal generation of cAMP or cGMP, but significantly reversed the inhibitory effects of NA (1 mM) and high KCl (60 mM) on cAMP and cGMP production. 5 EGCG inhibited the enzymatic activity of all the cyclic nucleotide PDE isoenzymes present in vascular tissue, being more effective on PDE2 (IC 50 B17) and on PDE1 (IC 50 B25). 6 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 [Ca 2 þ ] i .

Hydrogenosome Metabolism Is the Key Target for Antiparasitic Activity of Resveratrol against Trichomonas vaginalis

“…The data were examined by one-way analysis of variance (ANOVA) followed by a Tukey-Kramer test for multiple comparisons, and differences were considered significant at an ␣ value of 0.05. The concentration of drugs that caused a 50% inhibition of the response (IC 50 ) was estimated by nonlinear regression analysis (GraphPad Prism software; GraphPad, San Diego, CA, USA) from the concentration-response curves obtained in each case (34).…”

(-)-Epigallocatechin Gallate Inhibits the Pacemaker Activity of Interstitial Cells of Cajal of Mouse Small Intestine

“…In vascular system, EGCG showed seemingly contradictory actions on vascular tissues, such as a vasorelaxant activity (Chen et al, 2000;Alvarez et al, 2006) and a contractile behavior (Alvarez-Castro et al, 2004), that could be completely opposite reaction. And in small intestine, EGCG inhibits the motility of smooth muscle cells where a cGMP-dependent mechanism may partly be involved (Huang et al, 2006).…”

“…The effect of EGCG seems to be mediated by an increase of cytosolic cAMP and cGMP concentrations: This is via inhibition of various cyclic nucleotide phosphodiesterase (PDE) isoforms (Alvarez et al, 2006). Also, many authors suggested that cGMP plays important roles in mouse intestinal ICC.…”

Mitochondrial Abnormalities in Down Syndrome: Pathogenesis, Effects and Therapeutic Approaches

“…EGCG modulates key regulators of mitochondrial metabolism such as Sirt1 activity [142] and cAMP levels [143,144] in addition to being a specific and safe inhibitor of the Hsa21 gene DYRK1A, a kinase protein involved in brain development and in the control of synaptic plasticity [145]. This makes EGCG an interesting candidate drug for the treatment of DS phenotype.…”