Resistance arteries have a key role in the control of local blood flow. They are able to remodel in response to chronic increases in flow during growth, exercising or in ischemic diseases. Flow-mediated remodelling is governed by the endothelium. The incidence of metabolic syndrome increases with age and these 2 risk factors reduce endothelium integrity, because of an inflammatory process. We hypothesized that inflammation possibly through the induction of cycloxygenase-2 (COX2), might affect remodeling in old obese rats. In 12-month old obese and lean Zucker rats mesenteric resistance arteries were alternatively ligated in vivo so that one artery was submitted to high flow (HF), compare to normal flow (NF) vessels.

After 21 days, outward hypertrophic remodelling in HF arteries occurred in obese rats (498±20 in HF arteries vs 443±18μm in NF arteries, P<0.01), not in lean rats (454±17 vs 432±14, NS; n=12 per group). Endothelium-dependent (acetylcholine)-relaxation (AMR) was reduced in obese compare to lean rats. AMR was reduced by NO-synthesis blockade (L-NAME) in all groups and eNOS expression was higher in HF than in NF arteries without difference between lean and obese rats. Indomethacin further reduced AMR in HF from obese rats without significantly affecting arteries from lean animals. As COX2 immunostaining and expression level was evidenced in arteries from obese rats, COX2 inhibition (NS398) was tested on AMR. NS398 significantly reduced AMR in HF arteries in obese rats only. In obese rats chronically treated (3 weeks) with NS398 outward remodelling did not occurred in HF arteries.

Thus, COX2 preserved arterial remodelling in response to a chronic rise in blood flow in old obese rats. This adaptation is in favor of a better tissue perfusion.