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• W2038669656 abstract "Introduction: At birth, pulmonary artery (PA) blood flow increases 8–10 fold and PA pressure falls by 50% within 24 hours. The mechanisms responsible for postnatal adaptation of the pulmonary circulation remain incompletely understood. High serum endothelin-1 (ET-1) levels are found in infants with persistent pulmonary hypertension of the newborn. We hypothesized that chronic intrauterine pulmonary hypertension (PHT) potentiates agonist induced increase of cytosolic calcium concentration ([Ca2+]i) in fetal PA smooth muscle cells(SMC). Methods: Chronic intrauterine pulmonary hypertension was induced by intrauterine ligation of the ductus arteriosus (DA) in late-gestation fetal lambs. 7–10 days following DA ligation, animals were euthanized. Distal PAs (>4th generation) were removed from the lung and PA SMC were isolated and maintained in normoxic (95%O2) primary culture. Age-matched non-PHT controls were sacrificed at ∼132 days gestation and cells were cultured in the same manner. Fluorescence microscopy using fura-2 was used to determine the effect of ET-1 (10−6 -10−8 M) on PA SMC [Ca2+]i from PHT and control animals. To determine the effect of PHT on endothelin A and B (ETA and ETB) receptor mRNA expression, quantitative, internally controlled RT-PCR was performed on distal PAs and SMC in culture. Results: ET-1 (10−8 M) caused a monophasic increase in [Ca2+]i (206 +/- 47%, p < 0.01 vs baseline) above baseline in controls (n = 25), while PHT SMC [Ca2+]i did not increase significantly. When PHT SMC were treated with 10−6M ET-1, in those cells that responded, [Ca2+]i increased 174 +/- 81% above baseline(p < 0.01 vs baseline). Only 3/33 (9%) of PHT SMC responded to ET-1 compared to 90% of controls. Additionally, the duration of the increase in [Ca2+]i was longer in the PHT SMC: PHT SMC [Ca2+]i fell to baseline after 328 +/- 16 sec, where control [Ca2+]i fell to baseline after 117 sec. ETA and ETB receptor mRNA expression are both increased in PHT. Conclusions: PHT decreases PA SMC sensitivity to ET-1 by ∼100 fold, however, PHT increases the duration of the ET-1 induced increase in [Ca2+]i. We conclude that PHT prolongs the response of PA SMC to ET-1. This prolongation may lead to significant increases in PA SMC [Ca2+]i that results in attenuated postnatal adaptation of the pulmonary circulation." @default.
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• W2038669656 date "2003-10-01" @default.
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• W2038669656 title "Fetal pulmonary hypertension prolongs the endothelin-1 induced increase in pulmonary artery smooth muscle cell cytosolic calcium concentration" @default.
• W2038669656 doi "https://doi.org/10.1016/j.jss.2003.08.202" @default.
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