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Inhibition of voltage-gated, L-type Ca2+ (CaL) channels by clinical calcium channel blockers provides symptomatic improvement to some pediatric patients with pulmonary arterial hypertension (PAH). The present study investigated whether abnormalities of vascular CaL channels contribute to the pathogenesis of neonatal PAH using a newborn piglet model of hypoxia-induced PAH. Neonatal piglets exposed to chronic hypoxia (CH) developed PAH by 21 days, which was evident as a 2.1-fold increase in pulmonary vascular resistance in vivo compared with piglets raised in normoxia (N). Transpulmonary pressures (ΔPtp) in the corresponding isolated perfused lungs were 20.5 ± 2.1 mmHg (CH) and 11.6 ± 0.8 mmHg (N). Nifedipine reduced the elevated ΔPtp in isolated lungs of CH piglets by 6.4 ± 1.3 mmHg but only reduced ΔPtp in lungs of N piglets by 1.9 ± 0.2 mmHg. Small pulmonary arteries from CH piglets also demonstrated accentuated Ca2+-dependent contraction, and Ca2+ channel current was 3.94-fold higher in the resident vascular muscle cells. Finally, although the level of mRNA encoding the pore-forming α1C-subunit of the CaL channel was similar between small pulmonary arteries from N and CH piglets, a profound and persistent upregulation of the vascular α1C protein was detected by 10 days in CH piglets at a time when pulmonary vascular resistance was only mildly elevated. Thus chronic hypoxia in the neonate is associated with the anomalous upregulation of CaL channels in small pulmonary arteries in vivo and the resulting abnormal Ca2+-dependent resistance may contribute to the pathogenesis of PAH.

Background: In pregnancy, maternal serum concentrations of calcitriol significantly rise as a result of increased renal and placental contribution in order to assure calcium supply for the developing fetus. Considering that placenta is a site for vitamin D activation, and the versatility and potency of calcitriol, it is feasible that this hormone participates in fetal/placental development and physiology. In the present work we studied calcitriol actions upon human chorionic gonadotropin (hCG) secretion and expression in cultured trophoblasts, as well as vitamin D receptor (VDR) and CYP27B1 immunolocalization in placental villi.

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