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.