title: Chronic (-)-epicatechin improves vascular oxidative and inflammatory status but not hypertension in chronic nitric oxide-deficient rats.
abstract: The present study analysed the effects of the flavanol (-)-epicatechin in rats after chronic inhibition of NO synthesis with NG-nitro-L-arginine methyl ester (L-NAME), at doses equivalent to those achieved in the studies involving human subjects. Wistar rats were randomly divided into four groups: (1) control-vehicle, (2) L-NAME, (3) L-NAME-epicatechin 2 (L-NAME-Epi 2) and (4) L-NAME-epicatechin 10 (L-NAME-Epi 10). Rats were daily given by oral administration for 4 weeks: vehicle, (-)-epicatechin 2 or 10 mg/kg. Animals in the L-NAME groups daily received L-NAME 75 mg/100 ml in drinking-water. The evolution in systolic blood pressure and heart rate, and morphological and plasma variables, proteinuria, vascular superoxide, reactivity and protein expression at the end of the experiment were analysed. Chronic (-)-epicatechin treatment did not modify the development of hypertension and only weakly affected the endothelial dysfunction induced by L-NAME but prevented the cardiac hypertrophy, the renal parenchyma and vascular lesions and proteinuria, and blunted the prostanoid-mediated enhanced endothelium-dependent vasoconstrictor responses and the cyclo-oxygenase-2 and endothelial NO synthase (eNOS) up-regulation. Furthermore, (-)-epicatechin also increased Akt and eNOS phosphorylation and prevented the L-NAME-induced increase in systemic (plasma malonyldialdehyde and urinary 8-iso-PGF2α) and vascular (dihydroethidium staining, NADPH oxidase activity and p22phox up-regulation) oxidative stress, proinflammatory status (intercellular adhesion molecule-1, IL-1β and TNFα up-regulation) and extracellular-signal-regulated kinase 1/2 phosphorylation. The present study shows for the first time that chronic oral administration of (-)-epicatechin does not improve hypertension but reduced pro-atherogenic pathways such as oxidative stress and proinflammatory status of the vascular wall induced by blockade of NO production.
authors.affiliation: Department of Pharmacology, School of Pharmacy, University of Granada, 18071 Granada, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Gómez-Guzmán
authors.forename: Rosario
authors.initials: R
authors.lastname: Jiménez
authors.forename: Manuel
authors.initials: M
authors.lastname: Sánchez
authors.forename: Miguel
authors.initials: M
authors.lastname: Romero
authors.forename: Francisco
authors.initials: F
authors.lastname: O'Valle
authors.forename: Rocío
authors.initials: R
authors.lastname: Lopez-Sepulveda
authors.forename: Ana María
authors.initials: AM
authors.lastname: Quintela
authors.forename: Pilar
authors.initials: P
authors.lastname: Galindo
authors.forename: María José
authors.initials: MJ
authors.lastname: Zarzuelo
authors.forename: Elvira
authors.initials: E
authors.lastname: Bailón
authors.forename: Eva
authors.initials: E
authors.lastname: Delpón
authors.forename: Francisco
authors.initials: F
authors.lastname: Perez-Vizcaino
authors.forename: Juan
authors.initials: J
authors.lastname: Duarte
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000517:prevention & control; D001794:Blood Pressure / Q000187:drug effects; D002392:Catechin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D051546:Cyclooxygenase 2 / Q000097:blood; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D006973:Hypertension; D006984:Hypertrophy; D007249:Inflammation / Q000188:drug therapy*; D018836:Inflammation Mediators / Q000097:blood; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D009206:Myocardium / Q000473:pathology; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000172:deficiency*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D011453:Prostaglandins / Q000378:metabolism; D011507:Proteinuria / Q000188:drug therapy; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation; D014652:Vascular Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D018836:Inflammation Mediators; D010936:Plant Extracts; D011453:Prostaglandins; D009569:Nitric Oxide; D002392:Catechin; D019001:Nitric Oxide Synthase; D051546:Cyclooxygenase 2; D019331:NG-Nitroarginine Methyl Ester