Disturbances in nitric oxide/cyclic guanosine monophosphate system in SHR/NDmcr-cp rats, a model of metabolic syndrome.
Metabolic syndrome is a cluster of metabolic abnormalities, including hypertension, hyperlipidemia, hyperinsulinemia, glucose intolerance and obesity. In such lifestyle-related diseases, impairment of nitric oxide (NO) production or bioactivity has been reported to lead to the development of atherogenic vascular diseases. Therefore, in the present study we investigated changes in the NO/cyclic guanosine monophosphate (cGMP) system in aortas of SHR/NDmcr-cp (cp/cp) rats (SHR-cp), a model of the metabolic syndrome. In aortas of SHR-cp, endothelium-dependent relaxations induced by acetylcholine and endothelium-independent relaxations induced by sodium nitroprusside were significantly impaired in comparison with Wistar-Kyoto rats. Furthermore, protein levels of soluble guanylyl cyclase and cGMP levels induced by sodium nitroprusside were significantly decreased. In contrast, protein levels of endothelium NO synthase and cGMP levels induced by acetylcholine were significantly increased, and plasma NO2 plus NO3 levels were also increased. The levels of lipid peroxide in plasma and the contents of 3-nitrotyrosine, a biomarker of peroxynitrite, in aortas were markedly increased. These findings indicate that in the aortas of SHR-cp, NO production from the endothelium is augmented, although the NO-induced relaxation response is impaired. Enhanced NO production may be a compensatory response to a variety of factors, including increases in oxidative stress.
Kagota
Satomi
S
Department of Pharmacology, School of Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya, Japan. skagota@mwu.mukogawa-u.ac.jp
Yamaguchi
Yu
Y
Tanaka
Naoko
N
Kubota
Yoko
Y
Kobayashi
Kyoko
K
Nejime
Namie
N
Nakamura
Kazuki
K
Kunitomo
Masaru
M
Shinozuka
Kazumasa
K
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism*; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D006152:Cyclic GMP / Q000378:metabolism*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000378:metabolism* / Q000503:physiopathology; D009569:Nitric Oxide / Q000097:blood / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
D001786:Blood Glucose; D008055:Lipids; D017392:Thiobarbituric Acid Reactive Substances; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D006152:Cyclic GMP; D000109:Acetylcholine