Published Online
on May 21, 2007

A more recent version of this article appeared on July 1, 2007

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Submitted on February 9, 2007
Revised on February 27, 2007

Flow-Induced Remodeling in Resistance Arteries From Obese Zucker Rats Is Associated With Endothelial Dysfunction

Céline Bouvet; Eric Belin de Chantemèle; Anne-Laure Guihot; Emilie Vessières; Arnaud Bocquet; Odile Dumont; Alain Jardel; Laurent Loufrani; Pierre Moreau; and Daniel Henrion^*

From the Institut National de la Santé et de la Recherche U771 (C.B., E.B.d.C., A.-L.G., E.V., A.B., O.D., A.J., L.L., D.H.), Centre National de la Recherche Scientifique UMR 6214, Université d’Angers, Angers, France; and the Faculté de Pharmacie (C.B., P.M.), Université de Montréal, Montréal Quebec, Canada.

^* To whom correspondence should be addressed. E-mail: daniel.henrion{at}univ-angers.fr.

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 µm 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.

Key words: resistance arteries • shear stress • NO • reactive oxygen species • mechanotransduction • obesity • metabolic syndrome

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