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

Hypertension - Tập 50 Số 1 - Trang 248-254 - 2007
Céline Bouvet1, Eric J. Belin de Chantemèle1, Anne‐Laure Guihot1, Emilie Vessières1, Arnaud Bocquet1, Odile Dumont1, Alain Jardel1, Laurent Loufrani1, Pierre Moreau1, Daniel Henrion1
1From 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.

Tóm tắt

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.

Từ khóa


Tài liệu tham khảo

10.1001/jama.286.10.1195

10.2337/diacare.27.5.1047

10.1161/01.atv.0000118015.26978.07

10.1016/j.amjcard.2005.06.048

10.1001/archinte.164.10.1066

10.1152/ajpheart.1997.273.4.H1699

10.1161/res.79.5.1015

10.1161/atvb.16.10.1256

10.1161/01.atv.0000254684.80662.44

10.1006/mvre.2002.2417

10.1006/mvre.1998.2083

Zanchi A, Delacretaz E, Taleb V, Gaillard R, Jeanrenaud B, Brunner HR, Waeber B. Endothelial function of the mesenteric arteriole and mechanical behaviour of the carotid artery in rats with insulin resistance and hypercholesterolaemia. J Hypertens. 1995; 13: 1463–1470.

10.1152/ajpheart.00818.2003

10.1096/fj.01-0505fje

10.1152/ajpheart.2001.281.3.H1380

10.1161/01.res.0000047505.11002.81

10.1007/BF02363917

10.1152/ajpheart.00074.2004

10.1161/01.hyp.13.6.896

10.1152/ajpheart.2001.281.3.H1304

10.1152/ajpheart.00118.2003

10.1152/ajpheart.00854.2003

Jin JS, Bohlen HG. Non-insulin-dependent diabetes and hyperglycemia impair rat intestinal flow-mediated regulation. Am J Physiol. 1997; 272: H728–H734.

10.1152/ajpheart.00235.2003

10.1161/01.atv.0000110785.96039.f6

10.1172/JCI118709

10.1152/ajpheart.1998.274.3.H874

10.1161/01.res.0000181759.63239.21

10.1161/atvb.20.9.2057

10.1161/circ.102.3.351

Thông tin
Thông tin xuất bản

Hypertension

Tập 50 Số 1

248-254

Thông tin tác giả