visceral obesity is a risk factor for cardiovascular diseases. Perivascular adipose tissue (PVAT) is a visceral fat depot close to the vessel wall which therefore could directly influence vascular reactivity. Diet-induced alterations in endothelium-dependent vascular reactivity have been well investigated. Diet-induced changes in endothelium-independent vascular reactivity have received less attention.

we studied in 5-month-old rats fed low-fat (LFD) or high-fat diet (HFD) from weaning vascular reactivity using phenylephrine (PE)-stimulated isolated endothelium-removed aortic rings without or with their PVAT (PVAT - or PVAT +, respectively),

HFD induced an increase in mesenteric and PVAT fat mass, and enhanced systemic and mesenteric AT Tbars while it decreased aortic and PVAT Tbars. When PVAT - rings were incubated with increasing doses of PE, maximal contraction and EC50 were not different between groups. The presence of PVAT decreased the maximal contraction to the same extent in rings obtained from LFD- or HFD-fed rats. Incubation with catalase suppressed the anticontractile properties of PVAT, indicating that this effect was mediated through H2O2. Transfer experiments of PVAT conditioned medium demonstrated that PVAT was the site of H2O2 synthesis.

In LFD PVAT- rings, oxidative stress-associated procontractile activity was generated by xanthine oxidase and cytochrome c oxidase. In HFD PVAT- rings oxidative stress-associated procontractile activity increased and was generated, in addition to the above-mentioned enzymes, by NADPH oxidase. Catalase-induced H2O2 dismutation had prorelaxing properties, comparable in rings obtained from LFD or HFD fed rats. Superoxide dismutase (SOD) was devoid of effect in LFD rings, whereas it had a prorelaxing activity in HFD rings. These observations suggest that, in addition to H2O2, O2.- has a procontractile activity in the aortic wall of HFD rats. In aorta HFD increased the mRNAs coding for NADPH oxidase (p47 phox, p67phox, and NOX4), xanthine oxidase, SOD and catalase, suggesting an increased dismutation activity.

PVAT modified the effect of the various drugs tested. The increased anticontractile activity of PVAT found after reactive oxygen species scavenging was reduced in HFD fed rats compared with LFD fed animals. Inhibition of O2.- dismutation resulting from DETC-induced SOD blocking led to a procontractile effect of PVAT in both groups, this effect being reduced in HFD compared to LFD rats. NADPH blockade did not affect the anticontractile properties of PVAT in both groups. Xanthine oxidase blockade amplified the anticontractile effect of PVAT in LFD animals while it reversed this effect in HFD rats. In rings obtained from LFD animals cytochrome c oxidase blockade reversed the anticontractile effect of PVAT in LFD animals whereas it was devoid of effect in HFD rats.

In PVAT, HFD increased the mRNAs coding for cytochrome c oxidase, glutathione peroxidase and UCP-1 and -3.

our data show that HFD-induced obesity was associated with NADPH-dependent increased oxidative stress-associated procontractile activity in the aortic wall. Such phenomenon was counteracted by enhanced dismutation activity in the aortic wall and decreased procontractile activity provided by the PVAT. As a consequence, these observations predict that any defect in the above-mentioned counterregulatory mechanisms can have deleterious functional consequences.