title: Ferulic acid-4-O-sulfate rather than ferulic acid relaxes arteries and lowers blood pressure in mice.
abstract: Consumption of foods rich in ferulic acid (FA) such as wholegrain cereals, or FA precursors such as chlorogenic acids in coffee, is inversely correlated with risk of cardiovascular disease and type 2 diabetes. As a result of digestion and phase II metabolism in the gut and liver, FA is converted predominantly into ferulic acid-4-O-sulfate (FA-sul), an abundant plasma metabolite. Although FA-sul is the main metabolite, very little has been reported regarding its bioactivities. We have compared the ex vivo vasorelaxing effect of FA and FA-sul (10-7-3.10-5M) on isolated mouse arteries mounted in tissue myographs. FA-sul, but not FA, elicited a concentration-dependent vasorelaxation of saphenous and femoral arteries and aortae. The FA-sul-mediated vasorelaxation was blunted by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, a soluble guanylate cyclase (sGC) inhibitor. The role of sGC was confirmed in femoral arteries isolated from sGCα1(-/-)knockout mice. Furthermore, 4-aminopyridine, a specific inhibitor of voltage-dependent potassium channels, significantly decreased FA-sul-mediated effects. In anesthetized mice, intravenous injection of FA-sul decreased mean arterial pressure, whereas FA had no effect, confirming the results obtained ex vivo. FA-sul is probably one of the major metabolites accounting for the blood pressure-lowering effects associated with FA consumption.
authors.affiliation: Department of Food Safety and Food Quality, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000 Gent, Belgium. Electronic address: evelien.vanrymenant@ugent.be.
authors.forename: Evelien
authors.initials: E
authors.lastname: Van Rymenant
authors.affiliation: Department of Food Safety and Food Quality, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000 Gent, Belgium. Electronic address: john.vancamp@ugent.be.
authors.forename: John
authors.initials: J
authors.lastname: Van Camp
authors.affiliation: Department of Pharmacology, Faculty of Medicine and Health Sciences, Ghent University, De Pintelaan 185, 9000 Gent, Belgium. Electronic address: bart.pauwels@ugent.be.
authors.forename: Bart
authors.initials: B
authors.lastname: Pauwels
authors.affiliation: Department of Pharmacology, Faculty of Medicine and Health Sciences, Ghent University, De Pintelaan 185, 9000 Gent, Belgium. Electronic address: charlotte.boydens@ugent.be.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Boydens
authors.affiliation: Department of Pharmacology, Faculty of Medicine and Health Sciences, Ghent University, De Pintelaan 185, 9000 Gent, Belgium. Electronic address: laura.vandendaele@ugent.be.
authors.forename: Laura
authors.initials: L
authors.lastname: Vanden Daele
authors.affiliation: Department of Food Safety and Food Quality, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000 Gent, Belgium.
authors.forename: Katrijn
authors.initials: K
authors.lastname: Beerens
authors.affiliation: Department of Biomedical Molecular Biology, Faculty of Sciences, Ghent University-VIB, Technologiepark 927, 9052 Gent, Belgium. Electronic address: peter.brouckaert@irc.ugent.be.
authors.forename: Peter
authors.initials: P
authors.lastname: Brouckaert
authors.affiliation: Department of Crop Protection, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000 Gent, Belgium. Electronic address: guy.smagghe@ugent.be.
authors.forename: Guy
authors.initials: G
authors.lastname: Smagghe
authors.affiliation: School of Food Science and Nutrition, University of Leeds, Leeds LS2 9JT, UK. Electronic address: a.kerimi@leeds.ac.uk.
authors.forename: Asimina
authors.initials: A
authors.lastname: Kerimi
authors.affiliation: School of Food Science and Nutrition, University of Leeds, Leeds LS2 9JT, UK. Electronic address: g.williamson@leeds.ac.uk.
authors.forename: Gary
authors.initials: G
authors.lastname: Williamson
authors.affiliation: Department of Food Safety and Food Quality, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000 Gent, Belgium. Electronic address: charlotte.grootaert@ugent.be.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Grootaert
authors.affiliation: Department of Pharmacology, Faculty of Medicine and Health Sciences, Ghent University, De Pintelaan 185, 9000 Gent, Belgium. Electronic address: johan.vandevoorde@ugent.be.
authors.forename: Johan
authors.initials: J
authors.lastname: Van de Voorde
mesh_terms: D000818:Animals; D001158:Arteries / Q000187:drug effects* / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects*; D003069:Coffee / Q000737:chemistry; D003373:Coumaric Acids / Q000494:pharmacology*; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D059808:Polyphenols / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D000071756:Soluble Guanylyl Cyclase / Q000235:genetics / Q000378:metabolism; D013463:Sulfuric Acid Esters / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects; D000067348:Whole Grains / Q000737:chemistry
chemical_list: D003069:Coffee; D003373:Coumaric Acids; D059808:Polyphenols; D015221:Potassium Channels; D013463:Sulfuric Acid Esters; C000625833:ferulic acid-4-O-sulfate; C004999:ferulic acid; D000071756:Soluble Guanylyl Cyclase
keywords: Blood pressure; Ferulic acid; Ferulic acid-4-O-sulfate; Mouse; Vasorelaxation