Endothelium-derived contracting factors mediate the Ang II-induced endothelial dysfunction in the rat aorta: preventive effect of red wine polyphenols

Abstract

Angiotensin II (Ang II)-induced hypertension is associated with vascular oxidative stress and an endothelial dysfunction. This study examined the role of reactive oxygen species (ROS) and endothelium-derived contracting factors in Ang II-induced endothelial dysfunction and whether these effects are prevented by red wine polyphenols (RWPs), a rich source of natural antioxidants. Rats were infused with Ang II for 14 days. RWPs were administered in the drinking water 1 week before and during the Ang II infusion. Arterial pressure was measured in conscious rats. Vascular reactivity was assessed in organ chambers and cyclooxygenase-1 (COX-1) and COX-2 expression by Western blot and immunofluorescence analyses. Ang II-induced hypertension was associated with blunted endothelium-dependent relaxations and induction of endothelium-dependent contractions in the presence of nitro-L-arginine in response to acetylcholine (Ach). These effects were not affected by the combination of membrane permeant analogs of superoxide dismutase and catalase but were abolished by the thromboxane A(2) (TP) receptor antagonist GR32191B and the COX-2 inhibitor NS-398. The COX-1 inhibitor SC-560 also prevented contractile responses to Ach. Ang II increased the expression of COX-1 and COX-2 in the aortic wall. RWPs prevented Ang II-induced hypertension, endothelial dysfunction, and upregulation of COX-1 and COX-2. Thus, Ang II-induced endothelial dysfunction cannot be explained by an acute formation of ROS reducing the bioavailability of nitric oxide but rather by COX-dependent formation of contracting factors acting on TP receptors. RWPs are able to prevent the Ang II-induced endothelial dysfunction mostly due to their antioxidant properties.

Effect of angiotensin II-induced arterial hypertension on the voltage-dependent contractions of mouse arteries

“…The latter shift in membrane potential was, at least partly, induced by reduced basal NO bio-availability in the vessel wall. Endothelial dysfunction is a common feature in AHT [23], leading to impaired NO synthesis and/or bioavailability [3,13,35,36,42]. We did, however, not find evidence for attenuated NO release evoked by acetylcholine or sensitivity of the VSMCs for exogenous NO.…”

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

“…Although the reduction in COX-derived metabolites caused by Provinols may suggest a reduction in COX activity, further studies are warranted to ascertain the effects of Provinols on COX enzymes' activity. Consistent with our findings, a previous study from Kane et al [40] showed that red wine polyphenols reduced angiotensin II-induced COX-2 overexpression in rat vessels. Previous publications have also reported an inhibitory effect of red wine extract and tea polyphenols on COX-2 activity [20, 38].…”

The Protective Effect of Antioxidants Consumption on Diabetes and Vascular Complications

“…with antioxidant properties is actually a real asset in the prevention of chronic diseases, while the importance of prevention should not be underestimated. All publications by Dal et al demonstrated the interest of the use of natural antioxidants (red wine polyphenols) to prevent and treat diseases with endothelial dysfunction related to oxidative stress [62,64,213,471,472]. Moreover, our recent works carried out on in vitro and in vivo models of metabolic disorders have allowed us not only to involve oxidative stress in the pathophysiology of disorders but also to demonstrate that natural antioxidant compounds help to prevent or reduce complications (polyphenols from green tea and red wine [442,473], red cabbage, Dal S, under publication).…”