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(Hypertension. 2007;50:248.)
© 2007 American Heart Association, Inc.

Sixth International Workshop on Structure and Function of the Vascular System

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; 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.

Correspondence to Daniel Henrion, Department of Integrated Neurovascular Biology, UMR Centre National de la Recherche Scientifique 6214, Institut National de la Santé et de la Recherche 771, Faculté de Médecine, 49045 Angers, France. E-mail daniel.henrion{at}univ-angers.fr

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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