Open AccessTwo isoforms of cyclooxygenase contribute to augmented endothelium‐dependent contractions in femoral arteries of 1‐year‐old rats 1
Author(s) -
SHI Yi,
MAN Ricky YK,
VANHOUTTE Paul M
Publication year - 2008
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2008.00749.x
Subject(s) - endothelium , cyclooxygenase , nitric oxide , chemistry , nitric oxide synthase , medicine , endocrinology , thromboxane a2 , prostaglandin h2 , thromboxane , contraction (grammar) , receptor , biochemistry , biology , platelet , enzyme
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 N ω ‐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.