Nitric oxide inhibits serotonin-induced calcium release in pulmonary artery smooth muscle cells.
Nitric oxide (NO) is a potent endothelium-derived pulmonary vasodilator. Serotonin (5-HT; 10-50 microM) 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. The 5-HT-induced increase in [Ca2+]i was characterized by a transient (because of Ca2+ release from intracellular stores) followed by a plateau (because of 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 Ca(2+)-containing or Ca(2+)-free solution, 5-HT also induced Ca2+ oscillations. Pretreatment of the cells with 10 microM 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 (approximately 0.3 microM) 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 Ca(2+)-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.
Yuan
X J
XJ
Department of Medicine, University of Maryland School of Medicine, Baltimore 21201, USA.
Bright
R T
RT
Aldinger
A M
AM
Rubin
L J
LJ
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003600:Cytosol / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000494:pharmacology*; D009991:Oscillometry; D009994:Osmolar Concentration; D011651:Pulmonary Artery / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D012701:Serotonin / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects
D002121:Calcium Channel Blockers; D007211:Indoles; D009569:Nitric Oxide; D012701:Serotonin; D002110:Caffeine; D002118:Calcium; C000543:cyclopiazonic acid