Impairment of the vascular relaxation and differential expression of caveolin-1 of the aorta of diabetic + db/+ db mice

In this study, we compared the endothelium-dependent and -independent relaxation of the isolated thoracic aorta of control (+ db/+ m) and diabetic (+ db/+ db) (C57BL/KsJ) mice. The gene expression (mRNA and protein) level of the muscarinic M 3 receptors, endothelial nitric oxide synthase (eNOS) and...

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Published in:European journal of pharmacology 2006-09, Vol.546 (1), p.134-141
Main Authors: Lam, Tze Yan, Seto, Sai Wang, Lau, Yee Man, Au, Lai Shan, Kwan, Yiu Wa, Ngai, Sai Ming, Tsui, Kwong Wing
Format: Article
Language:English
Subjects:
Acetylcholine
Acetylcholine - pharmacology
Animals
Aorta
Aorta, Thoracic - chemistry
Aorta, Thoracic - drug effects
Aorta, Thoracic - physiopathology
Biological and medical sciences
Blood Glucose - metabolism
Blotting, Western
Caveolin 1 - analysis
Caveolin-1
Cromakalim - pharmacology
db/+ db mice
Diabetes Mellitus, Type 2 - blood
Diabetes Mellitus, Type 2 - metabolism
Diabetes Mellitus, Type 2 - physiopathology
Diabetes. Impaired glucose tolerance
Dose-Response Relationship, Drug
Endocrine pancreas. Apud cells (diseases)
Endocrinopathies
Endothelium, Vascular - physiopathology
Endothelium-dependent relaxation
Enzyme Inhibitors - pharmacology
Etiopathogenesis. Screening. Investigations. Target tissue resistance
Female
Insulin - blood
Isoproterenol - pharmacology
Medical sciences
Mice
Mice, Inbred C57BL
NG-Nitroarginine Methyl Ester - pharmacology
Nitric Oxide Synthase Type II - analysis
Nitric Oxide Synthase Type III
Nitroprusside - pharmacology
Pharmacology. Drug treatments
Receptor, Muscarinic M3 - analysis
RNA, Messenger - analysis
Vasodilation - drug effects
Vasodilator Agents - pharmacology
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Summary:In this study, we compared the endothelium-dependent and -independent relaxation of the isolated thoracic aorta of control (+ db/+ m) and diabetic (+ db/+ db) (C57BL/KsJ) mice. The gene expression (mRNA and protein) level of the muscarinic M 3 receptors, endothelial nitric oxide synthase (eNOS) and caveolin-1 of the aorta was also evaluated. Acetylcholine caused a concentration-dependent, N G-nitro- l-arginine methyl-ester (20 μM)-sensitive relaxation, with ∼ 100% relaxation at 10 μM, in + db/+ m mice. In + db/+ db mice, the acetylcholine-induced relaxation was significantly smaller (maximum relaxation: ∼ 80%). The sodium nitroprusside-mediated relaxation was slightly diminished in + db/+ db mice, compared to + db/+ m mice. However, there was no significant difference in the isoprenaline- and cromakalim-induced relaxation observed in both species. The mRNA and protein expression levels of caveolin-1 were significantly higher in the aorta of + db/+ db mice. In contrast, there was no difference in the mRNA and protein expression levels of eNOS and muscarinic M 3 receptors between these mice. Our results demonstrate that the impairment of the acetylcholine-induced, endothelium-dependent aortic relaxation observed in + db/+ db mice was probably associated with an enhanced expression of caveolin-1 mRNA and protein.
ISSN:0014-2999
1879-0712
DOI:10.1016/j.ejphar.2006.07.003