Inhibition by arachidonate of cerebral arteriolar dilation from acetylcholine.

After topical application of arachidonate (200 micrograms/ml) on the brain surface of anesthetized cats equipped with cranial windows, the vasodilator response to topical acetylcholine (10(-7) M) was either abolished or converted to vasoconstriction. This effect of arachidonate was prevented by pretreatment with topical deferoxamine (1 mM) to chelate free iron and inhibit the generation of hydroxyl radical from the Haber-Weiss reaction. Posttreatment with deferoxamine or with the combination of superoxide dismutase and catalase did not reestablish the vasodilator response to acetylcholine. Using a bioassay preparation in which one cranial window served as the donor for endothelium-derived relaxing factor (EDRF) while the other window was used to assay EDRF, we found that arachidonate applied to the donor window inhibited the generation and/or release of EDRF. Arachidonate applied to the assay window did not influence the response to EDRF. The results show that arachidonate interferes with the vasodilator response to acetylcholine, primarily because it inhibits the generation and release of EDRF. This effect is caused by injury to the endothelium induced by hydroxyl radical.