Cyclooxygenase-2-Derived Prostaglandin F 2α

Abstract

See related article, pages 228–235 Soluble vasoactive factors derived from vascular endothelium modulate the tone of underlying smooth muscle cells. Stimulation of intact, ie, endothelialized, vessels with acetylcholine causes vasodilation by release of endothelium-derived relaxing factors (EDRFs), mostly NO and hyperpolarizing factor(s) (EDHF). The endothelium also produces contractile factors (EDCF) of different origin.1 Thus, any reduced endothelium-dependent relaxation or even vasoconstriction could result from either loss of EDRFs, (enhanced) generation of EDCFs, or a combination of both. EDCF-mediated vasoconstriction might prevail with increasing age, as well as disturbed endothelial function, for example, in hypertension1,2 or type 2 diabetes.3 In addition to reduced generation of vasodilator prostaglandins (PGs), such as PGI2, enhanced production of vasoconstrictor prostanoids has been described.4,5 Oxygen-derived free radicals and isoprostanes, generated by exaggerated oxidative stress, are further members of the EDCF family. Thus, EDCFs represent an inhomogeneous group of compounds with different chemical identity. In the few last years, vasocontractile prostanoids, generated by endothelial cyclooxygenase(s) (COX[s]), have come into focus as significant EDCFs.1 One reason for this is the upregulation of endothelial COXs and enzymes of PG-endoperoxide catabolism during the aging process and hypertension with enhanced generation of these compounds6,7; another reason is the low selectivity of prostanoids for their membrane receptors. Vasoconstrictor prostanoids act on vascular smooth muscle cells via the thromboxane-prostanoid (TP) receptor.8 However, reactive oxygen species and other primary PGs, including PGI2 at higher concentrations,9 may also activate this receptor and cause vasoconstriction. In this issue of Circulation Research , Wong and colleagues10 demonstrate generation of a …