@article{APS4250,
author = {Yi Shi and Ricky YK Man and Paul M Vanhoutte},
title = {Two isoforms of cyclooxygenase contribute to augmented endotheliumdependent contractions in femoral arteries of 1-year-old rats},
journal = {Acta Pharmacologica Sinica},
volume = {29},
number = {2},
year = {2016},
keywords = {},
abstract = {Aim: The present experiments were designed to study the changes in endothelium-dependent contractions with aging.
Methods: The rat femoral arteries of 20-week and 1-year-old rats with and without endothelium were suspended in organ chambers to record isometric tension. The production of oxygen-derived free radicals in the endothelium was measured with 2',7'-dichlorodihydrofluorescein diacetate (DCF) using confocal microscopy. Protein presences were determined by Western blotting.
Results: In the arteries from the 1-year-old rats, endothelium-dependent relaxations to A23187 were reduced, but the endothelium-dependent contractions to A23187 (in the presence of Nω-nitro-L-arginine methyl ester
hydrochloride [L-NAME; an inhibitor of nitric oxide synthase]) were augmented, demonstrating endothelial dysfunction with aging. Indomethacin normalized the responses, suggesting that a cyclooxygenase (COX)-dependent contraction is prominent in aging. The endothelium-dependent contractions were also prevented by terutroban (a blocker of thromboxane-prostanoid receptors), confirming the activation of thromboxane-prostanoid receptors on vascular smooth muscle. Valeryl salicylate and NS-398 (preferential inhibitors of COX-1 and COX-2, respectively) partially reduced the response, indicating that both COX-1 and COX-2 are involved. Western blotting confirmed the upregulation of both isoforms in the arteries of the 1-year-old rats. In the presence of L-NAME, A23187 increased the DCF fluorescence in the endothelium, demonstrating that the production of oxygen-derived free radicals contributes to endothelium-dependent contractions. The activity of catalase was reduced in the arteries with endothelium of 1-year-old rats, indicating that hydrogen peroxide is the likely mediator of increased oxidative stress in the aging endothelium.
Conclusion: Endothelium-dependent contractions are augmented with aging. Oxidative stress potentiates the response, and both COX-1 and COX-2 are involved.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/4250}
}