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: Manuel Gómez-Guzmán, Rosario Jiménez, Manuel Sánchez, María José Zarzuelo, Pilar Galindo, Ana María Quintela, Rocío López-Sepúlveda, Miguel Romero, Juan Tamargo, Félix Vargas, Francisco Pérez-Vizcaíno, Juan Duarte
• Journal: Free radical biology & medicine (Free Radic Biol Med) Vol. 52 Issue 1 Pg. 70-9 (Jan 01 2012) ISSN: 1873-4596 [Electronic] United States
• PMID: 22001745 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• Endothelin-1
• NF-E2-Related Factor 2
• Nfe2l2 protein, rat
• Sodium Chloride, Dietary
• Superoxides
• 8-epi-prostaglandin F2alpha
• Desoxycorticosterone
• Malondialdehyde
• Catechin
• Dinoprost
• NOS3 protein, human
• Nitric Oxide Synthase Type III
• NADPH Oxidases

Topics

• Animals
• Aorta (drug effects, metabolism)
• Blood Pressure (drug effects)
• Catechin (pharmacology)
• Desoxycorticosterone (adverse effects)
• Dinoprost (analogs & derivatives, urine)
• Endothelin-1 (antagonists & inhibitors, blood)
• Endothelium, Vascular (drug effects, metabolism)
• Hypertension (blood, chemically induced, complications, drug therapy)
• Male
• Malondialdehyde (blood)
• NADPH Oxidases (antagonists & inhibitors, blood)
• NF-E2-Related Factor 2 (agonists, metabolism)
• Nitric Oxide Synthase Type III (metabolism)
• Oxidative Stress (drug effects)
• Proteinuria (blood, chemically induced, complications, drug therapy)
• Rats
• Rats, Wistar
• Sodium Chloride, Dietary (adverse effects)
• Superoxides (antagonists & inhibitors, metabolism)