title: Epicatechin lowers blood pressure, restores endothelial function, and decreases oxidative stress and endothelin-1 and NADPH oxidase activity in DOCA-salt hypertension.
abstract: Flavanol-rich diets have been reported to exert beneficial effects in preventing cardiovascular diseases, such as hypertension. We studied the effects of chronic treatment with epicatechin on blood pressure, endothelial function, and oxidative status in deoxycorticosterone acetate (DOCA)-salt-induced hypertension. Rats were treated for 5 weeks with (-)-epicatechin at 2 or 10 mg kg(-1)day(-1). The high dose of epicatechin prevented both the increase in systolic blood pressure and the proteinuria induced by DOCA-salt. Plasma endothelin-1 and malondialdehyde levels and urinary iso-prostaglandin F(2α) excretion were increased in animals of the DOCA-salt group and reduced by the epicatechin 10 mg kg(-1) treatment. Aortic superoxide levels were enhanced in the DOCA-salt group and abolished by both doses of epicatechin. However, only epicatechin at 10 mg kg(-1) reduced the rise in aortic nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and p47(phox) and p22(phox) gene overexpression found in DOCA-salt animals. Epicatechin increased the transcription of nuclear factor-E2-related factor-2 (Nrf2) and Nrf2 target genes in aortas from control rats. Epicatechin also improved the impaired endothelium-dependent relaxation response to acetylcholine and increased the phosphorylation of both Akt and eNOS in aortic rings. In conclusion, epicatechin prevents hypertension, proteinuria, and vascular dysfunction. Epicatechin also induced a reduction in ET-1 release, systemic and vascular oxidative stress, and inhibition of NADPH oxidase activity.
authors: Department of Pharmacology, School of Pharmacy, School of Medicine, University of Granada, Granada, Spain.
authors: Manuel
authors: M
authors: Gómez-Guzmán
authors: Rosario
authors: R
authors: Jiménez
authors: Manuel
authors: M
authors: Sánchez
authors: María José
authors: MJ
authors: Zarzuelo
authors: Pilar
authors: P
authors: Galindo
authors: Ana María
authors: AM
authors: Quintela
authors: Rocío
authors: R
authors: López-Sepúlveda
authors: Miguel
authors: M
authors: Romero
authors: Juan
authors: J
authors: Tamargo
authors: Félix
authors: F
authors: Vargas
authors: Francisco
authors: F
authors: Pérez-Vizcaíno
authors: Juan
authors: J
authors: Duarte
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects*; D002392:Catechin / Q000494:pharmacology; D003900:Desoxycorticosterone / Q000009:adverse effects; D015237:Dinoprost / Q000031:analogs & derivatives / Q000652:urine; D019332:Endothelin-1 / Q000037:antagonists & inhibitors* / Q000097:blood; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D006973:Hypertension / Q000097:blood / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors* / Q000097:blood; D051267:NF-E2-Related Factor 2 / Q000819:agonists / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011507:Proteinuria / Q000097:blood / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar; D017673:Sodium Chloride, Dietary / Q000009:adverse effects; D013481:Superoxides / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D019332:Endothelin-1; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D017673:Sodium Chloride, Dietary; D013481:Superoxides; C075750:8-epi-prostaglandin F2alpha; D003900:Desoxycorticosterone; D008315:Malondialdehyde; D002392:Catechin; D015237:Dinoprost; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D019255:NADPH Oxidases