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

Abstract

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±12 mN in controls (n=5) versus 67.6±13 mN in balloon injured aortas from hypercholesterolemic rabbits (n=5); P