Obesity and Body Fat Distribution Induce Endothelial Dysfunction by Oxidative Stress: Protective Effect of Vitamin C
2001
Endothelial dysfunction has been reported in obese subjects, but its
mechanism has not been elucidated. We have therefore investigated 1 )
the possible relationship among BMI, waist-to-hip ratio (WHR), and
endothelium-dependent vasodilation and 2 ) whether oxidative stress
participates in endothelial dysfunction. We recruited 76 healthy subjects (50
men and 26 women aged 21-45 years) and measured their BMI (kg/m 2 ),
WHR, and insulin resistance (IR) estimated by the homeostasis model assessment
(HOMA). Endothelium-dependent and -independent vasodilation were assessed by
increasing doses of acetylcholine (ACh) (7.5, 15, and 30 μg ·
ml -1 · min -1 ) and sodium nitroprusside (SNP)
(0.8, 1.6, and 3.2 μg · ml -1 · min -1 )
during saline and vitamin C coinfusion (24 mg/min). The effects of
cyclooxygenase activity were evaluated by a dose-response curve to
intrabrachial coinfusion of ACh and indomethacin (500 μg/min). Three
different groups have been identified according to their BMI: group A (BMI
<25), consisting of 10 men and 5 women; group B (BMI between 25 and 29),
consisting of 16 men and 8 women; and group C (BMI ≥30), consisting of 24
men and 13 women. Obese subjects had significantly lower forearm blood flow
(FBF) during ACh infusions (means ± SD): 19.8 ± 2.8, 10.8
± 2.7, and 6.5 ± 1.8 ml · 100 ml -1 tissue
· min -1 ( P < 0.0001) for groups A, B, and C,
respectively. SNP caused comparable increments in FBF in all groups.
Regression analysis revealed a significant negative correlation between BMI
( r = -0.676, P r = -0.631, P r = -0.695, P <
0.0001), HOMA-IR ( r = -0.633, P < 0.0001), and percent
peak increase in FBF during ACh infusion. In obese subjects, both vitamin C
and indomethacin increased the impaired vasodilating response to ACh, whereas
the SNP effect was unchanged. In conclusion, in obese subjects, ACh-stimulated
vasodilation is blunted, and the increase in FBF is inversely related to BMI,
WHR, fasting insulin, and HOMA-IR. The effects of both vitamin C and
indomethacin on impaired ACh-stimulated vasodilation support the hypothesis
that oxidative stress contributes to endothelial dysfunction in human
obesity.
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
31
References
325
Citations
NaN
KQI