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Caloric restriction and resveratrol attenuate doxorubicin‐induced vascular dysfunction in old rat mesenteric arteries
Author(s) -
Whidden Melissa Ann,
Kirichenko Nataliya,
Dutta Debapriya,
Xu Jinze,
Leeuwenburgh Christiaan,
Tumer Nihal
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1195.10
Subject(s) - mesenteric arteries , oxidative stress , medicine , resveratrol , doxorubicin , endothelial dysfunction , endocrinology , antioxidant , endothelium , vascular smooth muscle , malondialdehyde , pharmacology , chemistry , chemotherapy , artery , smooth muscle , biochemistry
Doxorubicin (DOX) is associated with oxidant‐induced damage to the endothelium and vascular dysfunction. Both caloric restriction (CR) and resveratrol (Res) have been shown to lower levels of oxidative stress and slow aging. So, we examined CR and Res alone and in combination on DOX‐induced vascular dysfunction in old mesenteric arteries (MA). 26 month male F‐344xBN rats were divided into: ad libitum (AL), AL+DOX, 20% CR, CR+DOX, Res, Res+DOX, CR+Res, and CR+Res+DOX. Over 6 wks rats consumed a 20% CR diet while Res (5 mg/kg/day) was given in pellets. DOX (10 mg/kg BW) was administered 24 hrs prior to sacrifice. Concentration‐response curves to Ach (10–9–10–5 M) with and without L‐NAME were evaluated in pressurized MAs. Endothelium‐mediated relaxation was significantly reduced in DOX (38 ± 4%) when compared with AL (76 ± 2%) rats (P<0.001). Alone, both 20% CR and Res attenuated the DOX‐induced reduction in dilation; 20% CR (56 ± 3%, P<0.05) and Res (70 ± 4%, P<0.01). There was no additive protection from DOX when treatments were used together. L‐NAME decreased responses to Ach in AL and treatment arteries and inhibited the reduced responses in the DOX MAs. These findings demonstrate that both antioxidant treatments contribute to the attenuation of vascular dysfunction found with DOX, however, Res appears to be more protective to the vascular system. Supported by NIH AG17994, 1P30AG02874, Department of Veteran Affairs.