Mechanism of potentiation by polyphenols of contraction in human vein-engineered media.

The potential of natural dietary polyphenols in the treatment of vascular diseases originating from veins has been suggested in the literature. However, the mechanisms involved to explain the effects of polyphenols are not yet elucidated. Therefore, the aim of this study was to investigate the mechanisms by which polyphenols from red wine (Provinols) modulated contraction in human veins. We took advantage of a human model previously reported as a new tool for pharmacological research, using tissue-engineered techniques allowing the production of vascular media based exclusively on human smooth muscle cells. Thus human tissue-engineered vascular media (TEVM) were produced with cells originating from umbilical cord vein. TEVM were treated with either vehicle or Provinols. Results showed that treatment of TEVM with Provinols significantly potentiated the contractile responses induced by histamine and bradykinin. The potentiating effect of Provinols was not associated with an enhancement of histamine-induced increase in cytosolic calcium; rather, it implied the presence of a Ca(2+)-independent signaling pathway. Pharmacological studies indicated that action of Provinols took place at the level of phospholipase A(2)-Rho-kinase pathway and was associated with an enhancement of myosin light chain kinase activity. These results, obtained using the human TEVM, bring new insights to explain the regulation of venous contraction by polyphenols.

Wine polyphenols stimulate superoxide anion production to promote calcium signaling and endothelial-dependent vasodilatation.

The present study was aimed to evaluate the mechanisms involved in the vasorelaxant effects of red wine polyphenol compounds (RWPC) in small mesenteric rat arteries. RWPC produce relaxation in small mesenteric arteries. This relaxant effect was abolished by endothelial denudation, NO-synthase blockade with L-NAME and partial depolarization with KCl or L-NAME plus KCl. Incubation with the reactive oxygen species scavenger, superoxide dismutase (SOD) plus catalase, or inhibition of NAD(P)H-dependent oxidoreductases with diphenyleneiodonium also inhibited RWPC induced vascular relaxation. Application of RWPC elicited a transient increase in intracellular calcium concentration ([Ca2+]i) in bovine aortic endothelial cells (BAEC), which was attenuated by a mixture of SOD and catalase. Incubation of BAEC with RWPC increased the SOD inhibitable production of O2-. These results suggest the involvement of O2- in the [Ca2+]i increase evoked by RWPC, leading to the activation of enzymes involved in the release of endothelial relaxant factors and subsequent vasodilatation of resistance arteries.

Polyphenolic compounds from Cognac induce vasorelaxation in vitro and decrease post-ischaemic cardiac infarction after an oral administration.

The effects of Cognac polyphenolic compounds (CPC) on aorta and isolated heart, the consequences of oral administration on haemodynamic parameters, vascular reactivity and cardiac recovery after ischaemia were investigated. CPC induced an endothelium-dependent vasorelaxation on rat-isolated aorta. This effect was prevented by the nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine-methyl ester, but not by the cyclo-oxygenase inhibitor, indomethacin, suggesting the implication of NO pathway. On isolated rat hearts, CPC induced positive inotropic, chronotropic, and lusitropic effect at 10(-4)-10(-2) g/L while at 10(-1) g/L, it had negative lusitropic effect and other parameters returned to baseline values. Oral administration of 40 mg/kg of CPC for 2 weeks did not modify systolic blood pressure and heart rate of rats throughout the treatment. CPC treatment did not affect ex vivo response of isolated thoracic aorta either to the contractile agent noradrenaline or to the endothelial-relaxant agent, acetylcholine. Isolated hearts from treated rats were submitted to 30-min global ischaemia followed by 120 min of reperfusion. Post-ischaemic recovery of functional cardiac parameters was not modified by treatment with CPC. Infarct size measured after the reperfusion in heart from CPC-treated rats was significantly decreased in comparison with hearts from control group. We conclude that in vitro, CPC had NO-dependent vasorelaxant effects and stimulated cardiac function. Oral treatment with CPC appeared to have no impact in vivo on blood pressure, heart rate of the rats or on cardiac contractility ex vivo; however, it could decrease the infarct size after an ischaemia-reperfusion.

Wine polyphenols decrease blood pressure, improve NO vasodilatation, and induce gene expression.

The effects of short-term oral administration of red wine polyphenolic compounds on hemodynamic parameters and on vascular reactivity were investigated in rats. Endothelial function and vascular smooth muscle contractility were studied in association with the induction of gene expression in the vascular wall. Rats were treated daily for 7 days by intragastric administration of either 5% glucose or red wine polyphenolic compounds (20 mg/kg). Administration of these compounds produced a progressive decrease in systolic blood pressure, which became significantly different on day 4. Aortas from rats treated with red wine polyphenolic compounds displayed increased endothelium-dependent relaxation to acetylcholine that was related to increased endothelial NO activity and involved a mechanism sensitive to superoxide anion scavengers. However, no increase in whole-body oxidative stress has been observed in rats treated with red wine polyphenolic compounds, as shown by plasma glutathione assay. Also, in the aorta, red wine polyphenolic compounds increased the expression of cyclooxygenase-2 and increased the release of endothelial thromboxane A(2), which compensated for the extraendothelial NO-induced hyporeactivity in response to norepinephrine, resulting from enhanced inducible NO synthase expression. The present study provides evidence that short-term oral administration of red wine polyphenolic compounds produces a decrease in blood pressure in normotensive rats. This hemodynamic effect was associated with an enhanced endothelium-dependent relaxation and an induction of gene expression (of inducible NO synthase and cyclooxygenase-2) within the arterial wall, which together maintain unchanged agonist-induced contractility. These effects of red wine polyphenolic compounds may be a potential mechanism for preventing cardiovascular diseases.

[Moderate alcohol consumption and cardiovascular diseases]. / Consommation modérée d'alcool et maladies cardiovasculaires.

While excessive ethanol consumption can result in higher rate of morbidity and mortality resulting from several diseases including cancer and cirrhosis, epidemiological studies suggest that moderate alcohol ingestion reduces the risk of cardiovascular diseases. However, the precise mechanisms by which moderate alcohol consumption protects against coronary heart disease (CHD) is not fully understood. Epidemiological studies suggest that alcohol consumption influences several risk factors for CHD including blood pressure, plasma cholesterol levels, platelet function, and fibrinolytic parameters, preventing both vascular thrombosis and occlusion. Turning to molecular and cellular levels, ethanol has been shown to act on several signal transduction mechanisms involve in the inhibition of smooth muscle cells proliferation and migration and in the activation of the release of vasoactive factors from vascular cells such as nitric oxide (NO). The latter is of importance since NO has been shown to possess antioxidant, antiaggregant properties, to regulate vascular tone and to inhibit both proliferation of smooth muscle cells and adhesion of leukocytes. Altogether, the above mentioned beneficial properties of moderate concentration of ethanol might help to explain the cardio- and vascular protection induced by ethanol. This review compels several bibliographic data concerning the cardiovascular effect of moderate alcohol consumption.

Endothelial no release caused by red wine polyphenols.

Epidemiological studies have suggested that moderate consumption of red wine might reduce the risk of cardiovascular disease. Red Wine Polyphenolic Compounds (RWPC), a complex extract obtained from red wine, causes endothelium-dependent vasorelaxation in rat aortic rings pre-contracted with noradrenaline. This effect is associated with marked formation of NO in the vessel (directly shown by electron paramagnetic resonance spectroscopy) and it is abolished by the NO synthase inhibitor N(G)-nitro-L-arginine methylester (300 microM). It is mimicked by some defined polyphenols (like the anthocyanin delphinidin) but not by others (malvidin, cyanidin, quercetin, catechin, epicatechin), despite close structures. In addition, RWPC causes an extracellular Ca(2+)-dependent increase in [Ca2+]i in endothelial but not in smooth muscle cells. The efficiency of RWPC in inducing NO production in the aorta and increase in [Ca2+]i, in endothelial cells is comparable to those of carbachol and bradykinine, respectively. These findings provide evidence that RWPC and polyphenols with selective structures can activate an undefined target in endothelial cells. The resulting increase in [Ca2+]i activation of NO-synthase and enhanced formation of NO may be involved in cardiovascular protection.

[Nodular lymphoid hyperplasia. Diffuse form extending from the duodenal bulb to the rectum, associated with agammaglobulinemia]. / Hyperplasie lymphoïde nodulaire. Forme diffuse étendue du bulbe duodénal au rectum, associée à une agammaglobulinémie.

The authors study a case of nodular lymphoid hyperplasia, extending from the duodenal bulb to the rectum, associated to an agammaglobulinemia; they observe the variations of the roentgenology appearance and the distribution of the elementary pictures; they discuss the meaning of the disease, the association or the evolution to a lymphoid carcinoma.

[Chronic lesions of the ulnar artery due to repeated occupational microtrauma complicated by acute arterial occlusion]. / Lésions chroniques de l'artère cubito-palmaire par microtraumatismes professionnels répétés compliquées d'oblitération artérielle aiguë.

A case of ulnar artery occlusion following repeated micro-trauma to one hand is reported. Following resection of the diseased portion of the artery and reconstruction with an interposition vein graft. The patient recovered normal use of the hand. Pathologic examination of the artery confirmed the operative findings. This case is typical of the vascular problems of the hand associated with certain occupations.