(-)-Epicatechin reduces blood pressure increase in high-fructose-fed rats: effects on the determinants of nitric oxide bioavailability.
This work investigated the blood pressure (BP)-lowering effect of the flavanol (-)-epicatechin in a model of metabolic syndrome. Rats were fed a regular chow diet without (Control) or with 10% (w/v) fructose in the drinking water (high fructose, HF) for 8 weeks. A subgroup of the HF-fed rats was supplemented with (-)-epicatechin 20 mg/kg body weight (HF-EC). Dietary (-)-epicatechin reverted the increase in BP caused by the fructose treatment. In aorta, superoxide anion production and the expression of the NADPH oxidase (NOX) subunits p47(phox) and p22(phox) were enhanced in the HF-fed rats. The increase was prevented by (-)-epicatechin. Similar profile was observed for NOX4 expression. The activity of aorta nitric oxide synthase (NOS) was increased in the HF group and was even higher in the HF-EC rats. These effects were paralleled by increased endothelial NOS phosphorylation at the activation site Ser1177. Among the more relevant mitogen-activated protein kinase pathways in vascular tissue, c-Jun-N-terminal kinase was shown to be activated in the aorta of the HF-fed rats, and (-)-epicatechin supplementation mitigated this activation. Thus, the results suggest that dietary (-)-epicatechin supplementation prevented hypertension in HF-fed rats, decreasing superoxide anion production and elevating NOS activity, favoring an increase in NO bioavailability.
Physical Chemistry-Institute for Molecular Biochemistry and Molecular Medicine (IBIMOL) School of Pharmacy and Biochemistry, University of Buenos Aires-National Council of Scientific and Technological Research (CONICET), Argentina.
Maria C
MC
Litterio
Department of Pathology, School of Medicine, National University of Cuyo and Institute of Medicine and Experimental Biology-CONICET, Mendoza, Argentina.
Marcela A
MA
Vazquez Prieto
Department of Biological Chemistry (IQUIFIB), School of Pharmacy and Biochemistry, University of Buenos Aires-National Council of Scientific and Technological Research (CONICET), Argentina.
Ana M
AM
Adamo
Physiology-Institute of Drug Chemistry and Metabolism (IQUIMEFA), School of Pharmacy and Biochemistry, University of Buenos Aires-National Council of Scientific and Technological Research (CONICET), Argentina.
Rosana
R
Elesgaray
Department of Nutrition, University of California at Davis, Davis, CA 95616, USA; Department of Environmental Toxicology, University of California at Davis, Davis, CA 95616, USA.
Patricia I
PI
Oteiza
Physical Chemistry-Institute for Molecular Biochemistry and Molecular Medicine (IBIMOL) School of Pharmacy and Biochemistry, University of Buenos Aires-National Council of Scientific and Technological Research (CONICET), Argentina. Electronic address: mgallean@ffyb.uba.ar.
Monica
M
Galleano
Physical Chemistry-Institute for Molecular Biochemistry and Molecular Medicine (IBIMOL) School of Pharmacy and Biochemistry, University of Buenos Aires-National Council of Scientific and Technological Research (CONICET), Argentina; Department of Nutrition, University of California at Davis, Davis, CA 95616, USA.
Cesar G
CG
Fraga
D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D000975:Antioxidants / Q000627:therapeutic use; D001013:Aorta, Thoracic / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D002392:Catechin / Q000627:therapeutic use*; D004040:Dietary Carbohydrates / Q000009:adverse effects; D019587:Dietary Supplements; D004730:Endothelium, Vascular / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D005632:Fructose / Q000009:adverse effects; D006973:Hypertension / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D020935:MAP Kinase Signaling System; D008297:Male; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009569:Nitric Oxide / Q000819:agonists* / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000037:antagonists & inhibitors / Q000378:metabolism
D000959:Antihypertensive Agents; D000975:Antioxidants; D004040:Dietary Carbohydrates; D013481:Superoxides; D005632:Fructose; D009569:Nitric Oxide; D002392:Catechin; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498911:Nox4 protein, rat; C515768:Cyba protein, rat; C060505:neutrophil cytosolic factor 1
Flavonoids; Fructose; Hypertension; Metabolic syndrome; Oxidants; Superoxide anion