TY - JOUR
T1 - High-fat diet-induced reduction in nitric oxide-dependent arteriolar dilation in rats
T2 - Role of xanthine oxidase-derived superoxide anion
AU - Erdei, Nóra
AU - Tóth, Attila
AU - Pásztor, Eniko T.
AU - Papp, Zoltán
AU - Édes, István
AU - Koller, Akos
AU - Bagi, Zsolt
PY - 2006
Y1 - 2006
N2 - Obesity frequently leads to the development of hypertension. We hypothesized that high-fat diet (HFD)-induced obesity impairs the endothelium-dependent dilation of arterioles. Male Wistar rats were fed with normal (control) or HFD (60% of saturated fat, for 10 wk). In rats with HFD, body weight, mean arterial blood pressure, and serum insulin, cholesterol, and glucose were elevated. In isolated gracilis muscle arterioles (diameter: ∼160 μm) of HFD, rat dilations to ACh (at 1 μM, maximum: 83 ± 3%) and histamine (at 10 μM, maximum: 16 ± 4%) were significantly (P < 0.05) decreased compared with those of control responses (maximum: 90 ± 2 and 46 ± 4%, respectively). Dilations to the NO donor sodium nitroprusside were similar in the two groups. Inhibition of NO synthesis by Nω-nitro-L-arginine methyl ester reduced ACh-and histamine-induced dilations in control arterioles but had no effect on microvessels of HFD rats. The superoxide dismutase mimetic Tiron or xanthine oxidase inhibitor allopurinol enhanced ACh (maximum: 90 ± 2 and 93 ± 2%, respectively)- and histamine (maximum: 30 ± 7 and 37 ± 8%, respectively)-induced dilations in HFD arterioles, whereas the NAD(P)H oxidase inhibitor apocynin had no significant effect. Correspondingly, in carotid arteries of HFD rats, an enhanced superoxide production was shown by lucigenin-enhanced chemiluminescence, in association with an increased xanthine oxidase, but not NAD(P)H oxidase activity. In addition, a marked xanthine oxidase immunostaining was detected in the endothelial layer of the gracilis arterioles of HFD, but not in control rats. These findings suggest that, in obese rats, NO mediation of endothelium-dependent dilation of skeletal muscle arterioles is reduced because of an enhanced xanthine oxidase-derived superoxide production. These alterations demonstrate substantial dysregulation of arteriolar tone by the endothelium in HFD-induced obesity, which may contribute to disturbed tissue blood flow and development of increased peripheral resistance.
AB - Obesity frequently leads to the development of hypertension. We hypothesized that high-fat diet (HFD)-induced obesity impairs the endothelium-dependent dilation of arterioles. Male Wistar rats were fed with normal (control) or HFD (60% of saturated fat, for 10 wk). In rats with HFD, body weight, mean arterial blood pressure, and serum insulin, cholesterol, and glucose were elevated. In isolated gracilis muscle arterioles (diameter: ∼160 μm) of HFD, rat dilations to ACh (at 1 μM, maximum: 83 ± 3%) and histamine (at 10 μM, maximum: 16 ± 4%) were significantly (P < 0.05) decreased compared with those of control responses (maximum: 90 ± 2 and 46 ± 4%, respectively). Dilations to the NO donor sodium nitroprusside were similar in the two groups. Inhibition of NO synthesis by Nω-nitro-L-arginine methyl ester reduced ACh-and histamine-induced dilations in control arterioles but had no effect on microvessels of HFD rats. The superoxide dismutase mimetic Tiron or xanthine oxidase inhibitor allopurinol enhanced ACh (maximum: 90 ± 2 and 93 ± 2%, respectively)- and histamine (maximum: 30 ± 7 and 37 ± 8%, respectively)-induced dilations in HFD arterioles, whereas the NAD(P)H oxidase inhibitor apocynin had no significant effect. Correspondingly, in carotid arteries of HFD rats, an enhanced superoxide production was shown by lucigenin-enhanced chemiluminescence, in association with an increased xanthine oxidase, but not NAD(P)H oxidase activity. In addition, a marked xanthine oxidase immunostaining was detected in the endothelial layer of the gracilis arterioles of HFD, but not in control rats. These findings suggest that, in obese rats, NO mediation of endothelium-dependent dilation of skeletal muscle arterioles is reduced because of an enhanced xanthine oxidase-derived superoxide production. These alterations demonstrate substantial dysregulation of arteriolar tone by the endothelium in HFD-induced obesity, which may contribute to disturbed tissue blood flow and development of increased peripheral resistance.
KW - Allopurinol
KW - Endothelium
KW - High-fat diet
KW - Metabolic syndrome
KW - Microvessel
KW - Nitric oxide
KW - Superoxide
KW - Xanthine oxidase
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U2 - 10.1152/ajpheart.00389.2006
DO - 10.1152/ajpheart.00389.2006
M3 - Article
C2 - 16798827
AN - SCOPUS:33751171952
SN - 0363-6135
VL - 291
SP - H2107-H2115
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
IS - 5
ER -