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

Research output: Contribution to journalArticlepeer-review

62 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)248-254
Number of pages7
JournalHypertension
Volume50
Issue number1
DOIs
StatePublished - Jul 2007

Keywords

  • Mechanotransduction
  • Metabolic syndrome
  • NO
  • Obesity
  • Reactive oxygen species
  • Resistance arteries
  • Shear stress

ASJC Scopus subject areas

  • Internal Medicine

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