259 Altered reactivity to norepinephrine through COX-2 induction by vascular injury in hypercholesterolemic rabbits

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• 作者：Magnus B&auml ; ck¹ ([Orateur]) ; Nabil Foudi² ; Mario Rienzo² ; Charles Brink² ; Jean-Baptiste Michel² ; Xavier Norel²
• 刊名：Archives of Cardiovascular Diseases Supplements
• 出版年：2010
• 出版时间：January 2010
• 年：2010
• 卷：2
• 期：1
• 页码：84
• 全文大小：83 K

文摘

Although long term use of cyclooxygenase (COX)-2 inhibitors may be associated with increased cardiovascular risk, their effects on vascular reactivity in atherosclerosis has remained largely unexplored. The aim of the present study was to evaluate the role of COX-2 induced by an atherosclerotic process, in the local control of vascular tone. To this end, New Zealand White rabbits were fed 0.3 % cholesterol for 3 weeks before being subjected to balloon injury of the abdominal aorta. After another 2 weeks, the aorta was removed and used for organ bath experiments and immunohistochemistry, and the prostaglandins released were measured using enzyme immunoassays. Hypercholesterolemia and vascular injury significantly increased the thickness of the intimal layer, which was associated with an induction of COX-2 immunoreactivity throughout the aortic wall. In these preparations, a significant decrease of the maximal contractions induced by norepinephrine was observed: 89.3¡À12 mN in controls (n=5) versus 67.6¡À13 mN in balloon injured aortas from hypercholesterolemic rabbits (n=5); P<0,05. The norepinephrine-induced contractions of atherosclerotic preparations were restored by the COX inhibitors DuP-697 (0.5 ¦Ìmol/L) and indomethacin (1.7 ¦Ìmol/L), to similar contractions as was observed in aortic preparations derived from healthy rabbits. Norepinephrine stimulation of the abdominal aorta was accompanied by increased levels of prostaglandin I₂ in atherosclerotic (1,39¡À0,11 ¦Ìg/mg, n=3) compared with normal aorta (0,53¡À0,17 ¦Ìg/mg, n=3, P<0,05). Selective COX-2 inhibition significantly decreased the prostaglandin I₂ release from atherosclerotic aorta, but had no effect on the prostaglandin release from aortic preparations derived from normal rabbits. These observations suggest that the local induction of COX-2 during atherosclerosis decreased the sensitivity to norepinephrine, and that COX-2 inhibitors may locally increase vascular reactivity at sites of atherosclerotic lesions.