Nitric oxide inhibits serotonin-induced calcium release in
pulmonary artery smooth muscle cells.
Yuan, Xiao-Jian, Rose T. Bright, Ann M. Aldinger, and Lewis J. Rubin.
Department of Medicine, Division of Pulmonary and Critical Care
Medicine; Department of Physiology, University of Maryland School of
Medicine, Baltimore, Maryland 21201
APStracts 3:0156L, 1996.
Nitric oxide (NO) is a potent endothelium-derived pulmonary
vasodilator. Serotonin (5-HT, 10-50 [mu]M) constricts pulmonary
artery (PA) by releasing Ca2+ from intracellular stores and promoting
Ca2+ influx through Ca2+ channels in PA smooth muscle cells (PASMC).
The effect of NO on 5-HT-induced increase in cytosolic free Ca2+
concentration ([Ca2+]i) in rat PASMC was investigated to elucidate
whether inhibition of agonist-mediated Ca2+ rise is involved in the
NO-mediated pulmonary vasodilation. 5-HT-induced increase in [Ca2+]i
was characterized by a transient (due to Ca2+ release from
intracellular stores) followed by a plateau (due to Ca2+ influx).
Removal of extracellular Ca2+ eliminated the 5-HT-induced [Ca2+]i
plateau, but insignificantly affected the [Ca2+]i transient. In some
of the PASMC bathed in the Ca2+-containing or Ca2+-free solution, 5
-HT also induced Ca2+ oscillations. Pretreatment of the cells with 10
[mu]M cyclopiazonic acid (CPA) abolished, whereas 10 mM caffeine
negligibly affected, the 5-HT-induced [Ca2+]i transients in the
absence of external Ca2+. Authentic NO (0.3 [mu]M) reversibly
diminished 5-HT-induced [Ca2+]i transients, but augmented CPA-induced
Ca2+ release in the absence of extracellular Ca2+. NO also
significantly inhibited 5-HT-induced [Ca2+]i plateau in PASMC bathed
in Ca2+-containing solution, suggesting that NO inhibits both
agonist-induced Ca2+ release from the CPA-sensitive Ca2+ stores and
Ca2+ influx from extracellular fluid. These data suggest that NO
-induced inhibition of the evoked increases in [Ca2+]i and
augmentation of Ca2+ sequestration into intracellular stores in PASMC
are involved in the mechanisms by which NO causes pulmonary
vasodilation.
Received 15 February 1996; accepted in final form 26 August 1996.
APS Manuscript Number L49-6.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 19 September 1996