Chronic intrauterine pulmonary hypertension increases capacitative calcium entry in fetal pulmonary artery smooth muscle cells.
Oxygen causes perinatal pulmonary dilatation. Although fetal pulmonary artery smooth muscle cells (PA SMC) normally respond to an acute increase in oxygen (O2) tension with a decrease in cytosolic calcium ([Ca2+]i), an acute increase in O2 tension has no net effect on [Ca(2+)](i) in PA SMC derived from lambs with chronic intrauterine pulmonary hypertension (PHTN). The present experimental series tests the hypothesis that an acute increase in O2 tension decreases capacitative calcium entry (CCE) in normal, but not hypertensive, fetal PA SMC. PA SMC were isolated from late-gestation fetal lambs after either ligation of the ductus arteriosus (PHTN) or sham (control) operation at 127 days gestation. PA SMC were isolated from the distal PA (>or=4th generation) and maintained under hypoxic conditions ( approximately 25 Torr) in primary culture. After fura 2 loading, apparent [Ca2+]i in PA SMC was determined as the ratio of 340- to 380-nm fluorescence intensity. Under both hypoxic and normoxic conditions, cyclopiazonic acid (CPA) increased [Ca2+]i more in PHTN than in control PA SMC. CCE was determined in PA SMC under hypoxic and normoxic conditions, after superfusion with zero extracellular Ca2+ and intracellular store depletion with CPA, followed by superfusion with Ca2+-containing solution, in the presence of the voltage-operated calcium channel blockade. CCE was increased in PHTN compared with control PA SMC under conditions of both acute and sustained normoxia. Transient receptor potential channel gene expression was greater in control compared with PHTN PA SMC. PHTN may compromise perinatal pulmonary vasodilation, in part, by modulating PA SMC CCE.
Resnik
Ernesto R
ER
Division of Pediatric Pulmonary and Critical Care Medicine, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA.
Keck
Maggie
M
Sukovich
David J
DJ
Herron
Jean M
JM
Cornfield
David N
DN
D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D005315:Fetal Diseases / Q000378:metabolism*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000196:embryology / Q000378:metabolism*; D007231:Infant, Newborn; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D010547:Persistent Fetal Circulation Syndrome / Q000378:metabolism; D011247:Pregnancy; D011651:Pulmonary Artery / Q000166:cytology / Q000378:metabolism*; D012756:Sheep; D050051:Transient Receptor Potential Channels / Q000502:physiology
D015220:Calcium Channels; D050051:Transient Receptor Potential Channels; D002118:Calcium