Putting the vasoactive effects of COX-2-derived prostanoids into clinical perspective

Ever since the recognition that the selective inhibitor of cyclooxygenase (COX)-2, rofecoxib, increases the risk for adverse cardiovascular events, enormous attention has been given to the mechanisms underlying these adverse vascular effects of the coxibs.1,2 Many recent studies that have investigated the biological consequences of COX-2 inhibition in the vasculature have focussed either on the prothrombotic side effects of decreased endothelial prostacyclin production during selective COX-2 blockade3,4 or on detrimental effects of such an intervention on atherosclerosis.5,6 Although such studies have greatly broadened our understanding of the pathophysiological roles of COX-2-mediated prostanoid production in vascular biology, the important vasodilatory functions of COX-2-derived prostanoids have been somewhat eclipsed by them.Foudi et al. presents data that address the topic of detrimental vascular effects of COX-2 inhibition from this different, yet important, point of view.7 They show in isolated human internal mammary arteries (IMA) that under conditions of acute septic inflammation, which is induced by simultaneous administration of interleukin-1β (IL-1β) and lipopolysaccharide (LPS), COX-2 is upregulated and produces prostacyclin and prostaglandin E2 (PGE2) rather than thromboxane A2 (TxA2). COX-2 expression is shown to be enhanced not only in the intima, but also in the smooth muscle cell-containing media of the vasculature. When vasoconstriction is induced by norepinephrine in the IMA preparations, COX-2 inhibition leads … Corresponding author. Tel: +49 89 5160 2111; fax: +49 89 5160 2410. E-mail address : florian.kroetz{at}med.uni-muenchen.de