Acute hypoxia increases cytosolic calcium in fetal pulmonary artery smooth muscle cells.
We studied the effect of acute hypoxia on the cytosolic calcium concentration ([Ca2+]i) of fetal vascular smooth muscle cells (SMC) from late gestation fetal lambs. We tested the following hypotheses: 1) fetal pulmonary artery (PA) SMC sense hypoxia; 2) hypoxia stimulates transmembrane Ca2+ influx causing increased basal [Ca2+]i and Ca2+ responses to pharmacological vasoconstrictors; and 3) the response is unique to SMC from small (near resistance) PA. Fetal SMC were isolated from the proximal and distal pulmonary (DPA) and carotid arteries of late-gestation ovine fetuses, maintained in culture for 5-14 days prior to study, and studied with dual-excitation microfluorimetry using fura 2. Acute hypoxia caused a 233% increase in [Ca2+]i in distal PA SMC (P < 0.01), which was absent in low extracellular calcium bath. [Ca2+]i increased transiently in normoxic DPA SMC treated with angiotensin II, and oscillations in [Ca2+]i occurred (amplitude > or = 30 nM). In hypoxic DPA SMC the increase in [Ca2+]i was sustained and oscillations were attenuated or absent. [Ca2+]i in proximal PA SMC did not change with exposure to acute hypoxia and carotid artery SMC [Ca2+]i decreased by 13% (P < 0.05). We conclude that fetal SMC isolated from the DPA of late-gestation ovine fetuses directly sense decreased oxygen tension with an increase in [Ca2+]i that is dependent on the entry of extracellular Ca2+.
Cornfield
D N
DN
Department of Pediatrics, Children's Hospital, Denver Colorado.
Stevens
T
T
McMurtry
I F
IF
Abman
S H
SH
Rodman
D M
DM
D000208:Acute Disease; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002339:Carotid Arteries / Q000166:cytology / Q000196:embryology; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism*; D005333:Fetus / Q000166:cytology / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000196:embryology*; D011651:Pulmonary Artery / Q000166:cytology / Q000196:embryology*
D000804:Angiotensin II; D002118:Calcium