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Abnormal Endothelium Dependent Antioxidant Activity in Zucker Obese Rats with Insulin Resistance
Author(s) -
Katakam Prasad VG,
Snipes James A,
Tulbert Christina D,
Miller Allison W,
Busija David W
Publication year - 2006
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.20.4.a300-b
Subject(s) - reactive oxygen species , oxidative stress , nitric oxide , insulin resistance , antioxidant , medicine , endothelium , endocrinology , chemistry , sodium nitroprusside , endothelial dysfunction , insulin , biochemistry
Oxidative stress has been implicated in the cardiovascular dysfunction associated with insulin resistance (IR) and diabetes. We investigated the endothelial regulation of reactive oxygen species (ROS) generation in Zucker obese (ZO) rats with IR and control lean (ZL) rats. Methods ROS production was measured with redox‐sensitive fluroprobe 5‐(and‐6)‐chloromethyl‐2′, 7′ –dichlorodihydro fluorescein diacetate acetyl ester (CM‐H 2 DCFDA). Segments of aorta with (endo+) and without (endo‐) endothelium were loaded with CM‐H 2 DCFDA and fluorescence intensity was measured at baseline and in the presence of N‐nitro L‐arginine methyl ester (L‐NAME) or sodium nitroprusside (SNP; 10 −8 and 10 −6 mol/L). Results CM‐H 2 DCFDA‐fluorescence intensity normalized to the dry weight and ZL baseline (% baseline) was greater in ZO (159±18% Vs. ZL, p<0.05). Endothelial denudation resulted in increased ROS generation in ZL (154±21%, n=7 each; p<0.05) while ZO was unaffected (122±7%, n=7 each). L‐NAME treatment enhanced ROS in endo+ ZL (155±23%, n=6; p<0.05) while endo+ ZO was unaffected (86±13%, n=7). ROS production in Endo‐ aortic segments of both groups was unaffected by L‐NAME. SNP at both doses enhanced ROS in all groups. Conclusions Endothelium exhibits antioxidant activity in ZL that may likely involve nitric oxide (NO) synthase. However, an exogenous NO donor did not display antioxidant property. Importantly, the endothelium dependent antioxidant activity appears to be impaired in ZO. (Support: NIH grants HL‐30260, HL‐46558, HL‐50587, DK‐62372).