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

• 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
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2006.07.003

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.