title: Flow-induced remodeling in resistance arteries from obese Zucker rats is associated with endothelial dysfunction.
abstract: Chronic increases in blood flow increase arterial diameter and NO-dependent dilation in resistance arteries. Because endothelial dysfunction accompanies metabolic syndrome, we hypothesized that flow-mediated remodeling might be impaired in obese rat resistance arteries. Obese and lean Zucker rat mesenteric resistance arteries were exposed to chronic flow increases through arterial ligation in vivo: arteries exposed to high flow were compared with normal flow arteries. Diameter was measured in vitro in cannulated arteries using pressure arteriography. After 7 days, outward remodeling (diameter increased from 346+/-9 to 412+/-11 mum at 100 mm Hg) occurred in lean high-flow arteries. Endothelium-dependent tone was reduced in high-flow arteries from obese rats by contrast with lean animals. On the other hand, diameter enlargement occurred similarly in the 2 strains. The involvement of NO in endothelium-dependent dilation (evidenced by NO blockade) and endothelial NO synthase phosphorylation was smaller in obese than in lean rats. Superoxide anion and reduced nicotinamide-adenine dinucleotide phosphate oxidase subunit expression (p67phox and gp91phox) increased in obese rats and were higher in high-flow than in control arteries. Acute Tempol (a catalase mimetic), catalase plus superoxide dismutase, and l-arginine plus tetrahydrobiopterin restored endothelium-dependent dilation in obese rat normal and high-flow arteries to the level found in lean control arteries. Thus, flow-induced remodeling in obese resistance arteries was associated with a reduced endothelium-mediated dilation because of a decreased NO bioavailability and an excessive superoxide production. This dysfunction might have negative consequences in ischemic diseases in patients with obesity or metabolic syndrome.
authors.affiliation: Institut National de la Santé et de la Recherche U771, UMR Centre National de la Recherche Scientifique 6214, Université d'Angers, Angers, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Bouvet
authors.forename: Eric
authors.initials: E
authors.lastname: Belin de Chantemèle
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Guihot
authors.forename: Emilie
authors.initials: E
authors.lastname: Vessières
authors.forename: Arnaud
authors.initials: A
authors.lastname: Bocquet
authors.forename: Odile
authors.initials: O
authors.lastname: Dumont
authors.forename: Alain
authors.initials: A
authors.lastname: Jardel
authors.forename: Laurent
authors.initials: L
authors.lastname: Loufrani
authors.forename: Pierre
authors.initials: P
authors.lastname: Moreau
authors.forename: Daniel
authors.initials: D
authors.lastname: Henrion
mesh_terms: D000818:Animals; D001682:Biological Availability; D004730:Endothelium, Vascular / Q000503:physiopathology*; D008026:Ligation; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008638:Mesenteric Arteries / Q000503:physiopathology*; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009765:Obesity / Q000503:physiopathology*; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D011924:Rats, Zucker; D012039:Regional Blood Flow; D013481:Superoxides / Q000378:metabolism; D014655:Vascular Resistance; D014664:Vasodilation
chemical_list: D008562:Membrane Glycoproteins; D010750:Phosphoproteins; C079789:neutrophil cytosol factor 67K; D013481:Superoxides; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; C500593:Cybb protein, rat; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases