ASTROCYTE-DERIVED LIPOXYGENASE PRODUCT EVOKES ENDOTHELIUM-DEPENDENT RELAXATION OF THE BASILAR ARTERY

The goal of this study was to examine the possible production of vasoa ctive factors by astrocytes. We consistently observe that rat astrogli al cells in suspension produce marked relaxation when added to precont racted rings of intact (but not endothelium-denuded) rabbit basilar ar tery. The ultimate mediator of this relaxation was endothelium-derived nitric oxide whose synthesis is activated by an as yet unidentified f actor(s) produced tonically by astrocytes. The factor is relatively st able, and is not arachidonate, or a product of cyclooxygenase or P450 metabolism. Based upon studies with selective inhibitors, the factor a ppears to result from 12- or 15-lipoxygenase metabolism, the products of which are known to be vasoactive. In a separate series of experimen ts, astrocyte-conditioned medium stimulated the production of citrulli ne from L-arginine by nitric oxide synthase in bovine aortic endotheli al cells. The possible significance for central nervous system (CNS) p athophysiology of an astrocyte-derived vasodilator is discussed. (C) 1 994 Wiley-Liss, Inc.