New perspectives of nitric oxide donors in cardiac arrest and cardiopulmonary resuscitation treatment

Nitric oxide (NO) is often used to treat heart failure accompanied with pulmonary edema. According to present knowledge, however, NO donors are contraindicated when systolic blood pressure is less than 90 mmHg. Based on recent findings and our own clinical experience, we formulated a hypothesis about the new breakthrough complex lifesaving effects of NO donors in patients with cardiac arrest and cardiopulmonary resuscitation therapy. It includes a direct hemodynamic effect of NO donors mediated through vasodilation of coronary arteries in cooperation with improvement of cardiac function and cardiac output through reversible inhibition of mitochondrial complex I and mitochondrial NO synthase, followed by reduction in reactive oxygen species and correction of myocardial stunning. Simultaneously, an increase in vascular sensitivity to sympathetic stimulation could lead to an increase in diastolic blood pressure. Confirmation of this hypothesis in clinical practice would mean a milestone in the treatment for cardiac arrest and cardiopulmonary resuscitation

Dual effect of polyphenolic compounds on cardiac Na+/K+-ATPase during development and persistence of hypertension in ratsThis article is one of a selection of papers published in a special issue on Advances in Cardiovascular Research.

The enzyme kinetics of cardiac Na+/K+-ATPase were used for characterizing the ATP- and Na+-binding sites after administration of red wine polyphenolic compounds (Provinol) during developing and sustained hypertension. Hypertension was induced in rats (LN group) by the nitric oxide synthase inhibitor NG-nitro-l-arginine methyl ester (l-NAME, 40 mg·kg–1·day–1). Provinol (40 mg·kg–1·day–1) was applied during developing hypertension (LNPF4 group) and sustained hypertension (LNPF7/3 group). Provinol reduced the number of active Na+/K+-ATPase molecules in cardiac tissue, as indicated by decreased Vmax values (by 33% in LNPF4 and 26% in LNPF7/3 compared with LN). Concerning qualitative properties of the enzyme, Provinol induced different effects on the ATP- and Na+-binding sites of Na+/K+-ATPase. The ATP-binding site was impaired by Provinol, as indicated by increased Km value (by 52% in LNPF4 vs. LN), suggesting worsened utilization of substrate by the enzyme. In sustained hypertension, however, Provinol had no..., On a utilisé la cinétique enzymatique de la Na+/K+-ATPase pour caractériser les sites de liaison de l’ATP et du Na+ après l’administration de composés polyphénoliques du vin rouge (Provinol) durant l’installation de l’hypertension et l’hypertension confirmée. On a induit l’hypertension chez des rats (groupe LN) par le biais de l’inhibiteur de la monoxyde d’azote synthase, l-NAME (40 mg·kg–1·jour–1). On a administré le Provinol (40 mg·kg–1·jour–1) durant l’installation de l’hypertension (LNPF4) et durant l’hypertension confirmée (LNPF7/3). Le Provinol a réduit le nombre de molécules actives de la Na+/K+-ATPase dans le tissu cardiaque, comme l’indique la diminution des valeurs de Vmax (de 33 % chez LNPF4 et de 26 % chez LNPF7/3 comparativement à celles du groupe LN). Du point de vue qualitatif, le Provinol a induit divers effets sur les sites de liaison de l’ATP et du Na+ de la Na+/K+-ATPase. Il a altéré le site de liaison de l’ATP, comme le montre l’augmentation de la valeur de Km (de 52 % chez le groupe L..

Red wine polyphenols correct vascular function injured by chronic carbon tetrachloride intoxication

The aim of the study was to evaluate the effect of red wine polyphenols extract Provinols™ on the development of cardiovascular injury in the model of carbon tetrachloride (CCl4) intoxication. We followed the thoracic aorta vasoactivity and left ventricle nitric oxide (NO) synthase activity in male Wistar rats. In the preventive experiment lasting for 12 weeks the control group, the group receiving CCl4 (0.5 ml/kg) two times a week subcutaneously, the group receiving Provinols™ (30 mg/kg/day) in drinking water and the group receiving CCl4+Provinols™ was used. In the recovery experiment, the initial 12 weeks of CCl4 treatment were followed by 3 weeks of spontaneous recovery or recovery with Provinols™. CCl4-intoxication resulted in the injury of vasoactivity which was demonstrated by the inhibition of acetylcholine-induced relaxation as well as noradrenaline-induced contraction. In the preventive as well as recovery experiment administration of polyphenols refreshed endothelium-dependent relaxant response and normalized inhibited contraction to adrenergic stimuli. Provinols™ treatment significantly increased NO-synthase activity in all groups. The results revealed beneficial effects of red wine polyphenols on vascular function injured by chronic CCl4 intoxication. The correction of endothelial function seems to be attributed to the activation of NO pathway by polyphenols

Red wine polyphenols prevent cyclosporine-induced nephrotoxicity at the level of the intrinsic apoptotic pathway

Flavonoids, polyphenol derivatives of plant origin, possess a broad range of pharmacological properties. A number of studies have found both pro/anti-apoptotic effects for many of these compounds. For these reasons we investigated whether Provinols flavonoids obtained from red wine, have anti-apoptotic properties. The investigations have been carried out in rats treated with Cyclosporine A (CsA). In particular, four groups of rats have been treated for 21 days with either olive oil (control group), with CsA, with Provinols, or with CsA and Provinols simultaneously. Oxidative stress, systolic blood pressure, body weight, biochemical parameters and different markers of pro/anti-apoptotic pathway were measured. CsA produced an increase of systolic blood pressure, a decrease in body weight, serum creatinine levels, urinary total protein concentration and creatinine clearance. Moreover, CsA induced renal alterations and the translocation of Bax and cytochrome c from cytoplasm to mitochondria and vice versa. These changes activated the caspase cascade pathway, that leads to morphological and biochemical features of apoptosis. Provinols restored morphological and biochemical alterations and prevented nephrotoxicity. In conclusion, this study may augment our current understanding of the controversial pro-/anti-apoptotic properties of flavonoids and their molecular mechanisms

Differential modulation of oxidative and nitrosative stress pathways by red wine polyphenols, ProvinolsTM, in tissues from Zucker fatty rats (fa/fa).

Date du colloque : 2009National audienc

Microparticles from patients with metabolic syndrome induce in vivo endothelial dysfunction and vascular hypo-reactivity by increasing oxidative and nitrosative stresses in mouse aorta

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Red wine polyphenols prevent metabolic and cardiovascular alterations associated with obesity in Zucker fatty rats (Fa/Fa)

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A phylogenetic approach to study the origin and evolution of plasmodesmata-localized glycosyl hydrolases family 17.

Colonization of the land by plants required major modifications in cellular structural composition and metabolism. Intercellular communication through plasmodesmata (PD) plays a critical role in the coordination of growth and cell activities. Changes in the form, regulation or function of these channels are likely linked to plant adaptation to the terrestrial environments. Constriction of PD aperture by deposition of callose is the best-studied mechanism in PD regulation. Glycosyl hydrolases family 17 (GHL17) are callose degrading enzymes. In Arabidopsis this is a large protein family, few of which have been PD-localized. The objective here is to identify correlations between evolution of this protein family and their role at PD and to use this information as a tool to predict the localization of candidates isolated in a proteomic screen. With this aim, we studied phylogenetic relationship between Arabidopsis GHL17 sequences and those isolated from fungi, green algae, mosses and monocot representatives. Three distinct phylogenetic clades were identified. Clade alpha contained only embryophytes sequences suggesting that this subgroup appeared during land colonization in organisms with functional PD. Accordingly, all PD-associated GHL17 proteins identified so far in Arabidopsis thaliana and Populus are grouped in this 'embryophytes only' phylogenetic clade. Next, we tested the use of this knowledge to discriminate between candidates isolated in the PD proteome. Transient and stable expression of GFP protein fusions confirmed PD localization for candidates contained in clade alpha but not for candidates contained in clade beta. Our results suggest that GHL17 membrane proteins contained in the alpha clade evolved and expanded during land colonization to play new roles, among others, in PD regulation

Microparticles from patients with metabolic syndrome induce vascular hypo-reactivity via Fas/Fas-ligand pathway in mice

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