title: Impairment of the vascular relaxation and differential expression of caveolin-1 of the aorta of diabetic +db/+db mice.
abstract: 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 microM)-sensitive relaxation, with approximately 100% relaxation at 10 microM, in +db/+m mice. In +db/+db mice, the acetylcholine-induced relaxation was significantly smaller (maximum relaxation: approximately 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.
authors.affiliation: Department of Pharmacology, The Chinese University of Hong Kong, Hong Kong SAR, PR China.
authors.forename: Tze Yan
authors.initials: TY
authors.lastname: Lam
authors.forename: Sai Wang
authors.initials: SW
authors.lastname: Seto
authors.forename: Yee Man
authors.initials: YM
authors.lastname: Lau
authors.forename: Lai Shan
authors.initials: LS
authors.lastname: Au
authors.forename: Yiu Wa
authors.initials: YW
authors.lastname: Kwan
authors.forename: Sai Ming
authors.initials: SM
authors.lastname: Ngai
authors.forename: Kwong Wing
authors.initials: KW
authors.lastname: Tsui
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000737:chemistry / Q000187:drug effects / Q000503:physiopathology*; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D051242:Caveolin 1 / Q000032:analysis*; D019806:Cromakalim / Q000494:pharmacology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007328:Insulin / Q000097:blood; D007545:Isoproterenol / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D052247:Nitric Oxide Synthase Type II / Q000032:analysis; D052250:Nitric Oxide Synthase Type III; D009599:Nitroprusside / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D043587:Receptor, Muscarinic M3 / Q000032:analysis; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D001786:Blood Glucose; D051242:Caveolin 1; D004791:Enzyme Inhibitors; D007328:Insulin; D012333:RNA, Messenger; D043587:Receptor, Muscarinic M3; D014665:Vasodilator Agents; D019806:Cromakalim; D009599:Nitroprusside; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D007545:Isoproterenol; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester