Flow-induced remodeling in resistance arteries from obese Zucker rats is associated with endothelial dysfunction

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 mu m 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.