title: Cocoa flavanols lower vascular arginase activity in human endothelial cells in vitro and in erythrocytes in vivo.
abstract: The availability of l-arginine can be a rate-limiting factor for cellular NO production by nitric oxide synthases (NOS). Arginase competes with NOS for l-arginine as the common substrate. Increased arginase activity has been linked to low NO levels, and an inhibition of arginase activity has been reported to improve endothelium-dependent vasorelaxation. Based on the above, we hypothesized that an increase in the circulating NO pool following flavanol consumption could be correlated with decreased arginase activity. To test this hypothesis we (a) investigated the effects of (-)-epicatechin and its structurally related metabolites on endothelial arginase expression and activity in vitro; (b) evaluated the effects of dietary flavanol-rich cocoa on kidney arginase activity in vivo; and (c) assessed human erythrocyte arginase activity following flavanol-rich cocoa beverage consumption in a double-blind intervention study with cross-over design. The results demonstrate that cocoa flavanols lower arginase-2 mRNA expression and activity in HUVEC. Dietary intervention with flavanol-rich cocoa caused diminished arginase activity in rat kidney and, erythrocyte arginase activity was lowered in healthy humans following consumption of a high flavanol beverage in vivo.
authors: Institute for Biochemistry and Molecular Biology I, Building 22.03, Heinrich-Heine-University Duesseldorf, Universitaetsstrasse 1, D-40225 Duesseldorf, Germany. schnorr@uni-duesseldorf.de
authors: Oliver
authors: O
authors: Schnorr
authors: Tatjana
authors: T
authors: Brossette
authors: Tony Y
authors: TY
authors: Momma
authors: Petra
authors: P
authors: Kleinbongard
authors: Carl L
authors: CL
authors: Keen
authors: Hagen
authors: H
authors: Schroeter
authors: Helmut
authors: H
authors: Sies
mesh_terms: D000328:Adult; D001119:Arginase / Q000032:analysis / Q000378:metabolism*; D002099:Cacao / Q000737:chemistry*; D002478:Cells, Cultured; D018592:Cross-Over Studies; D004311:Double-Blind Method; D042783:Endothelial Cells / Q000187:drug effects / Q000201:enzymology*; D004730:Endothelium, Vascular / Q000166:cytology; D004912:Erythrocytes / Q000187:drug effects / Q000201:enzymology*; D044948:Flavonols / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D014471:Umbilical Veins / Q000166:cytology
chemical_list: D044948:Flavonols; D001119:Arginase