A role for cyclooxygenase in aging-related changes of beta-adrenoceptor-mediated relaxation in rat aortas.
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 microM) were significantly reduced in 54-week-old aortas compared to 8-week. Addition of the non-selective COX inhibitors indomethacin (10 microM) or aspirin (10 microM) 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 prostaglandin F(1alpha)) 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(1alpha) 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.
Kang
Khong Bee
KB
School of Medical Sciences, RMIT University, P.O. Box 71, Bundoora, VIC 3083, Australia.
Rajanayagam
M A Sharmini
MA
van der Zypp
Andrea
A
Majewski
Henryk
H
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000375:Aging / Q000502:physiology*; D000818:Animals; D001013:Aorta, Thoracic / Q000502:physiology*; D001241:Aspirin / Q000494:pharmacology; D007150:Immunohistochemistry; D007213:Indomethacin / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects*
D011943:Receptors, Adrenergic, beta; D015121:6-Ketoprostaglandin F1 alpha; D011451:Prostaglandin-Endoperoxide Synthases; D007545:Isoproterenol; D001241:Aspirin; D007213:Indomethacin