Peroxynitrite modulates receptor-activated ca2+ signaling in
vascular endothelial cells..
Elliott, Stephen J.
Department of Pediatrics and the Cardiovascular Research Center,
Medical College of Wisconsin, Milwaukee WI 53226
APStracts 3:0045L, 1996.
Peroxynitrite (ONOO-) is formed from superoxide (O2-) and .NO. We have
previously reported that O2- does not alter endothelial cell Ca2+
signaling. To test whether .NO alters Ca2+ signaling, cells were
incubated with the .NO-donor, spermine NONOate. Neither spermine
NONOate nor S-nitroso-N-acetyl penicillamine (SNAP) altered
bradykinin-stimulated Ca2+ signaling. By contrast, SIN-1, which
generates ONOO- by releasing O2- and .NO essentially simultaneously,
significantly inhibited signaling. Initially, the inhibitory effect
of 1 mM SIN-1 was selective toward agonist-stimulated influx of
external Ca2+. At later timepoints, SIN-1 additionally depleted
internal stores of releasable Ca2+. When cells were coincubated with
SIN-1 plus superoxide dismutase, a technique designed to scavenge O2-
and convert SIN-1 to purely an .NO-donor compound, Ca2+ signaling was
identical to control. SIN-1C, the inactive metabolite of SIN-1, had
no effect on [Ca2+]i. This study demonstrates that exogenously
generated ONOO- modulates endothelial cell Ca2+ signaling, suggesting
that ONOO- is of biological relevance to vasoregulation.
Received 3 November 1995; accepted in final form 11 March 1996.
APS Manuscript Number L314-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 27 March 96