title: Thymoquinone improves aging-related endothelial dysfunction in the rat mesenteric artery.
abstract: Aging-related endothelial dysfunction is characterized by blunted nitric oxide (NO)- and endothelium-derived hyperpolarizing factor (EDHF)-mediated relaxations in arteries, which may be due, at least in part, to increased oxidative stress. Endothelial dysfunction will promote the initiation and development of major cardiovascular diseases such as atherosclerosis and hypertension. Thymoquinone (TQ) is the most active constituent of the volatile oil of Nigella sativa seeds with well-documented antioxidative properties and vasodilator effects. This study determined whether TQ improves the endothelial function in middle-aged rats. Control young rats (16 weeks) received solvent (ethanol, 3% v/v), and middle-aged rats (46 weeks) either solvent or TQ (10 mg/kg/day) in the drinking water. Mesenteric artery reactivity was determined in organ chambers, vascular oxidative stress by dihydroethidine and MitoSOX staining, and expression of target proteins by immunohistochemical staining. Aging-related blunted NO- and EDHF-mediated responses were associated with downregulation of endothelial NO synthase (eNOS) and calcium-activated potassium channels (SK(Ca) and IK(Ca)) expression. Endothelial dysfunction was also associated with oxidative stress and an upregulation of angiotensin II and AT1 receptor expressions. Intake of TQ for 14 days restored NO- and EDHF-mediated relaxations, normalized oxidative stress, the expression level of eNOS, SK(Ca), IK(Ca), and the components of the angiotensin system in the mesenteric artery of middle-aged rats. Thus, TQ improves endothelial function in aging, at least in part, through inhibition of oxidative stress and normalization of the angiotensin system. TQ may represent a novel therapeutic approach for aging-associated vascular diseases.
authors.affiliation: CNRS UMR 7213, Laboratoire de Biophotonique et Pharmacologie, Faculty of Pharmacy, University of Strasbourg, 74, route du Rhin, BP 60024, 67401 Illkirch, France. noureddine.idris-khodja@unistra.fr
authors.forename: Noureddine
authors.initials: N
authors.lastname: Idris-Khodja
authors.forename: Valérie
authors.initials: V
authors.lastname: Schini-Kerth
mesh_terms: D000375:Aging / Q000502:physiology*; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D016227:Benzoquinones / Q000494:pharmacology*; D001685:Biological Factors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D009569:Nitric Oxide / Q000494:pharmacology; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D024681:Potassium Channels, Calcium-Activated / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects
chemical_list: D016227:Benzoquinones; D001685:Biological Factors; D024681:Potassium Channels, Calcium-Activated; D017382:Reactive Oxygen Species; D044140:Receptor, Angiotensin, Type 1; C067410:endothelium-dependent hyperpolarization factor; D000804:Angiotensin II; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D007703:Peptidyl-Dipeptidase A; C003466:thymoquinone