Paradoxical Effect of Nonalcoholic Red Wine Polyphenol Extract, Provinols™, in the Regulation of Cyclooxygenases in Vessels from Zucker Fatty Rats (fa/fa)

The aim of this work was to study the vascular effects of dietary supplementation of a nonalcoholic red wine polyphenol extract, Provinols, in Zucker fatty (ZF) obese rats. ZF or lean rats received diet supplemented or not with Provinols for 8 weeks. Vasoconstriction in response to phenylephrine (Phe) was then assessed in small mesenteric arteries (SMA) and the aorta with emphasis on the contribution of cyclooxygenases (COX). Although no difference in vasoconstriction was observed between ZF and lean rats both in SMA and the aorta, Provinols affected the contribution of COX-derived vasoconstrictor agents. The nonselective COX inhibitor, indomethacin, reduced vasoconstriction in vessels from both groups; however, lower efficacy was observed in Provinols-treated rats. This was associated with a reduction in thromboxane-A2 and 8-isoprostane release. The selective COX-2 inhibitor, NS398, reduced to the same extent vasoconstriction in aortas from ZF and Provinols-treated ZF rats. However, NS398 reduced response to Phe only in SMA from ZF rats. This was associated with a reduction in 8-isoprostane and prostaglandin-E release. Paradoxically, Provinols decreased COX-2 expression in the aorta, while it increased its expression in SMA. We provide here evidence of a subtle and paradoxical regulation of COX pathway by Provinols vessels from obese rats to maintain vascular tone within a physiological range

Interleukin-10 controls the protective effects of circulating microparticles from patients with septic shock on tissue-engineered vascular media

During sepsis, inflammation can be orchestrated by the interaction between circulating and vascular cells that, under activation, release MPs (microparticles). Previously, we reported that increased circulating MPs in patients with sepsis play a pivotal role in ex vivo vascular function suggesting that they are protective against vascular hyporeactivity. The present study was designed to investigate the effects of MPs from patients with sepsis on the contractile response of TEVM (tissue-engineered vascular media). TEVM that were composed only of a media layer were produced by tissue engineering from human arterial SMCs (smooth muscle cells) isolated from umbilical cords. TEVM was incubated with MPs isolated from whole blood of 16 patients with sepsis. TEVM were incubated for 24 h with MPs and used for the study of vascular contraction, direct measurements of NO and O2- (superoxide anion) production by EPR and quantification of mRNA cytokine expression. MPs from patients with sepsis increased contraction induced by histamine in TEVM. This effect was not associated with inflammation, neither linked to the activation of NF-kappaB (nuclear factor kappaB) pathway nor to the increase in iNOS (inducible NO synthase) and COX (cyclo-oxygenase)-2 expression. In contrast, mRNA expression of IL (interleukin)-10 was enhanced. Then, we investigated the effect of IL-10 on vascular hyporeactivity induced by LPS (lipopolysaccharide). Although IL-10 treatment did not modify the contractile response in TEVM by itself, this interleukin restored contraction in LPS-treated TEVM. In addition, IL-10 treatment both prevented vascular hyporeactivity induced by LPS injection in mice and improved survival of LPS-injected mice. These findings show an association between the capacity of MPs from patients with sepsis to restore vascular hyporeactivity induced by LPS and their ability to increase IL-10 in the tissue-engineered blood vessel model

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

Peer reviewedPublisher PD

Provinols™ improve cardiac function in ZF rats.

<p>Echocardiography measurements of diastolic left ventricular dimension (LVDd), systolic left ventricular dimension (LVDs), cardiac output and fraction of ejection (A–D). Systolic blood pressure was evaluated using tail-cuff technique (E). Total arterial peripheral resistances were calculated from blood pressure and cardiac output (F). Values are means±SEM (<i>n</i> = 6). *<i>P</i><0.05 Zucker fatty (ZF) rats <i>vs.</i> lean rats; #<i>P</i><0.05 ZF+Provinols™ rats <i>vs.</i> ZF rats.</p

Provinols™ improve endothelial function in ZF rats.

<p>Acetylcholine (Ach)-induced relaxation in rat aorta (A), small mesenteric arteries (SMA) (B), SMA in the presence of inhibitors of EDHF and COX components (C) (apamine, APA; charybdotoxin, CTX; indomethacin, INDO), SMA in the presence of inhibitors of NO and COX components (D) (INDO, L-NAME). Results are expressed as a percentage of relaxation. Values are means±SEM (<i>n</i> = 6). *<i>P</i><0.05, ***<i>P</i><0.001 Zucker fatty (ZF) rats <i>vs.</i> lean rats; #<i>P</i><0.05, ###<i>P</i><0.001 ZF+Provinols™ rats <i>vs.</i> ZF rats.</p

Provinols™ improve metabolic parameters in ZF rats.

<p>Circulating levels of glucose (A), fructosamine (B), total cholesterol (C), ratio between LDL- and HDL-cholesterol (D), triglygerides (E), creatinin (F) and uric acid (G) were evaluated in fasting plasma of rats. Values are means±SEM (<i>n</i> = 11–12). *<i>P</i><0.05, **<i>P</i><0.01, ***<i>P</i><0.001 Zucker fatty (ZF) rats <i>vs.</i> lean rats; #<i>P</i><0.05, ###<i>P</i><0.001 ZF+Provinols™ rats <i>vs.</i> ZF rats.</p