title: Crataegus special extract WS(®)1442 prevents aging-related endothelial dysfunction.
abstract: Aging is associated with a markedly increased incidence of cardiovascular diseases due, in part, to the development of vascular endothelial dysfunction. The present study has evaluated whether the Crataegus special extract WS(®)1442 prevents the development of aging-related endothelial dysfunction in rats, and, if so, to determine the underlying mechanisms. Wistar rats received either a control diet or the same diet containing 100 or 300 mg/kg/day of WS(®)1442 from week 25 until week 65. Vascular reactivity was assessed in mesenteric artery rings using organ chambers, oxidative stress by dihydroethidine staining and cyclooxygenase-1 (COX-1) and -2 (COX-2) expression by immunohistochemistry. Acetylcholine-induced endothelium-dependent relaxations in mesenteric artery rings were blunted in 65-week-old rats compared to 16-week-old rats. This effect was associated with a marked reduction of the endothelium-derived hyperpolarizing factor (EDHF) component whereas the nitric oxide (NO) component was not affected. Aging was also associated with the induction of endothelium-dependent contractile responses to acetylcholine. Both aging-related impairment of endothelium-dependent relaxations and the induction of endothelium-dependent contractile responses were improved by the Crataegus treatment and by COX inhibitors. An excessive vascular oxidative stress and an upregulation of COX-1 and COX-2 were observed in the mesenteric artery of old rats compared to young rats, and these effects were improved by the Crataegus treatment. In conclusion, chronic intake of Crataegus prevented aging-related endothelial dysfunction by reducing the prostanoid-mediated contractile responses, most likely by improving the increased oxidative stress and the overexpression of COX-1 and COX-2.
authors.affiliation: CNRS UMR 7213, Faculty of Pharmacy, University of Strasbourg, Illkirch, France.
authors.forename: N
authors.initials: N
authors.lastname: Idris-Khodja
authors.forename: C
authors.initials: C
authors.lastname: Auger
authors.forename: E
authors.initials: E
authors.lastname: Koch
authors.forename: V B
authors.initials: VB
authors.lastname: Schini-Kerth
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D001685:Biological Factors / Q000378:metabolism; D001713:Biphenyl Compounds / Q000494:pharmacology; D027825:Crataegus; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology*; D006538:Heptanoic Acids / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D001685:Biological Factors; D001713:Biphenyl Compounds; D016861:Cyclooxygenase Inhibitors; D006538:Heptanoic Acids; D010936:Plant Extracts; D017382:Reactive Oxygen Species; C067410:endothelium-dependent hyperpolarization factor; D009569:Nitric Oxide; C007145:crataegus extract; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C060013:vapiprost; D007213:Indomethacin