AJP - Heart and Circulatory Physiology, Vol 270, Issue 4 1258-H1263, Copyright © 1996 by American Physiological Society
Singlet oxygen scavengers affect laser-dye impairment of endothelium-dependent responses of brain arterioles
W. I. Rosenblum and G. H. Nelson
Department of Pathology (Neuropathology), Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0017, USA.
This study investigates the possible role of singlet oxygen in accounting
for the inhibitory effect of laser-dye injury on endothelium-dependent
dilations. The combination of helium-neon (HeNe) laser (20-s exposure) and
intravascular Evans blue impairs endothelium-dependent dilation of mouse
pial arterioles by acetylcholine (ACh), bradykinin (BK), and calcium
ionophore A23187. Each has a different endothelium-derived mediator
(EDRFACh, EDRFBK, EDRFionophore, respectively). In this 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, complete or partial, at 60 min.
Dilations by sodium nitroprusside, an endothelium-independent dilator, were
not affected by laser-dye. When the singlet oxygen scavengers L-histidine
(10(-3) M) and L-tryptophan (10(-2) M) were added to the suffusate over the
site, the responses to ACh at 10 and 30 min were relatively intact, the
response to BK was partly 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 singlet oxygen generation by the endothelial cell (not by the
dye). We postulate further that destruction of EDRFACh by singlet oxygen is
responsible for laser-dye inhibition of ACh and that generation of the
radical must continue for > or = 30 min. On the other hand, the heat
injury itself is probably responsible for the elimination 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, account for the impaired response to
BK.
