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 M₃ 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 M₃ 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.