VITAMIN-E AMELIORATES ADVERSE-EFFECTS OF ENDOTHELIAL INJURY IN BRAIN ARTERIOLES

Endothelium-dependent dilation, produced by applying acetylcholine (AC h) to pial arterioles, was unaffected after 6 mo of a diet with zero v itamin E or 8 mo of a vitamin E-enriched diet. The enriched diet did n ot affect constriction produced by topically applied N-G-monomethyl-L- arginine, an inhibitor of the synthesis of endothelium-derived relaxin g factor (EDRF). EDRF mediates the response to ACh and is a basally re leased dilator and antiplatelet paracrine substance. Endothelial injur y produced by a helium-neon laser and Evans blue technique eliminates the response to ACh, but in vitamin E-enriched mice the response to AC h was unaffected by the injury. More prolonged exposure of the laser i nduces platelet adhesion/aggregation at the injured site. A significan tly longer exposure to the laser was required to initiate adhesion/agg regation in vitamin E-enriched mice. Because effects of endothelial da mage in this model are mediated at least in part by singlet oxygen pro duced by injured tissue (W. I. Rosenblum and G. H. Nelson, Am. J. Phys iol. 270 (Heart Circ. Physiol. 39): H1258-H1263, 1996.), we conclude t hat the antioxidant, radical-scavenging actions of vitamin E explain t he protective action of the vitamin E-enriched diet. However, raising vitamin E levels did not protect against putative adverse effects of n ormally occurring oxidants.