title: 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.
authors.affiliation: Département de Biophotonique et Pharmacologie, Faculté de Pharmacie, Université de Strasbourg, CNRS UMR 7213, 74 Route du Rhin, 67401 Illkirch, France.
authors.forename: Modou O
authors.initials: MO
authors.lastname: Kane
authors.forename: Nelly
authors.initials: N
authors.lastname: Etienne-Selloum
authors.forename: Soccoro V F
authors.initials: SV
authors.lastname: Madeira
authors.forename: Mamadou
authors.initials: M
authors.lastname: Sarr
authors.forename: Allison
authors.initials: A
authors.lastname: Walter
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Dal-Ros
authors.forename: Christa
authors.initials: C
authors.lastname: Schott
authors.forename: Thierry
authors.initials: T
authors.lastname: Chataigneau
authors.forename: Valérie B
authors.initials: VB
authors.lastname: Schini-Kerth
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects*; D016718:Arachidonic Acid / Q000378:metabolism; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology*; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology*; D059808:Polyphenols; D051381:Rats; D017208:Rats, Wistar; D014920:Wine / Q000032:analysis*
chemical_list: D005419:Flavonoids; D010636:Phenols; D059808:Polyphenols; D000804:Angiotensin II; D016718:Arachidonic Acid; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D000109:Acetylcholine