SINGLET OXYGEN SCAVENGERS AFFECT LASER-DYE IMPAIRMENT OF ENDOTHELIUM-DEPENDENT RESPONSES OF BRAIN ARTERIOLES

This study investigates the possible role of singlet oxygen in account ing for the inhibitory effect of laser-dye injury on endothelium-depen dent dilations. The combination of helium-neon (HeNe) laser (20-s expo sure) and intravascular Evans blue impairs endothelium-dependent dilat ion of mouse pial arterioles by acetylcholine (ACh), bradykinin (BK), and calcium ionophore A23187. Each has a different endothelium-derived mediator (EDRF(ACh), EDRF(BK), EDRF(ionophore), respectively). In thi s study, diameters at a craniotomy site were monitored in vivo with an image splitter-television microscope. The laser-dye injury, as usual, abolished the responses 10 and 30 min after injury, with recovery, co mplete or partial, at 60 min. Dilations by sodium nitroprusside, an en dothelium-independent dilator, were not affected by laser-dye. When th e singlet oxygen scavengers L-histidine (10(-3) M) and L-tryptophan (1 0(-2) M) were added to the suffusate over the site, the responses to A Ch at 10 and 30 min were relatively intact, the response to BK was par tly protected at 10 min only, and the response to ionophore was still totally impaired at 10 and 30 min. Lysine, a nonscavenging amino acid, had no protective effects with any dilator. We postulate that a heat- induced injury initiates a chain of events resulting in prolonged sing let oxygen generation by the endothelial cell (not by the dye). We pos tulate further that destruction of EDRF(Ach) by singlet oxygen is resp onsible for laser-dye inhibition of ACh and that generation of the rad ical must continue for greater than or equal to 30 min. On the other h and, the heat injury itself is probably responsible for the eliminatio n of the response to ionophore. Heat plus singlet oxygen generated by heat-damaged tissue may initially impair the response to BK, but by 30 min only the effects of some other factor, presumably heat injury, ac count for the impaired response to BK.