A role for cyclooxygenase in aging-related changes of β-adrenoceptor-mediated relaxation in rat aortas

被引:13
作者
Bee Kang, Khong [1 ]
Sharmini Rajanayagam, M. A. [1 ]
van der Zypp, Andrea [1 ]
Majewski, Henryk [1 ]
机构
[1] RMIT Univ, Sch Med Sci, Bundoora, Vic 3083, Australia
关键词
beta-adrenoceptor; age; endothelium; cyclooxygenase; prostacyclin; aorta;
D O I
10.1007/s00210-007-0153-y
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
beta-Adrenoceptor-mediated vasorelaxation decreases with age in various vascular beds. The present study investigated the roles of cyclooxygenase (COX) on beta-adrenoceptor vasorelaxation by isoprenaline in 8- and 54-week-old rat aortas. The vasorelaxation responses by isoprenaline (0.03-3 mu M) were significantly reduced in 54-week-old aortas compared to 8-week. Addition of the non-selective COX inhibitors indomethacin (10 mu M) or aspirin (10 mu M) restored isoprenaline vasorelaxation of 54-week-old aortas to levels found in 8-week-old aortas. This suggests the involvement of COX prostanoids in the age-related reduction of beta-adrenoceptor vasorelaxation. Immunohistochemistry revealed greater levels of COX-1 and COX-2 staining in 54-week-old aortas compared to 8-week with expression located mainly in medial smooth muscle. An age-linked increase in COX-1 and COX-2 protein was found in cremaster arterioles of 54-week-old rats (compared to 8-week) mainly in the endothelial layer. The age-related increase in COX-1 and COX-2 protein led to elevation of prostacyclin (measured as 6-keto prostagladin F-1 alpha) and thromboxane A(2) (measured as thromboxane B-2) in 54-week compared to 8-week-old aortas. Endothelium removal in 54-week aortas markedly reduced the 6-keto prostaglandin F-1 alpha level, thus suggesting an endothelial source for elevated prostacyclin. These findings in combination with the effects of COX inhibitors suggest that the age-related decrease in beta-adrenoceptor vasorelaxation by isoprenaline is due to an age-linked increase in COX expression, which elevates production of COX-derived vasoactive prostanoids.
引用
收藏
页码:273 / 281
页数:9
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