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Long-term hypoxia (LTH) has a profound effect on pulmonary arterial vasoconstriction in the fetus and adult. Dysregulation in Ca 2+  signaling is important during the development of LTH-induced pulmonary hypertension. In the present study, we tested the hypothesis that L-type Ca 2+  channels (Ca L ), which are voltage dependent and found in smooth, skeletal, and cardiac muscle, are important in the adaptation of pulmonary arterial contractions in postnatal maturation and in response to LTH. Pulmonary arteries were isolated from fetal or adult sheep maintained at low or high altitude (3,801 m) for &gt;100 days. The effects were measured using an L-type Ca 2+  channel opener FPL 64176 (FPL) in the presence or absence of an inhibitor, Nifedipine (NIF) on arterial contractions, intracellular Ca 2+  oscillations, and ryanodine receptor-driven Ca 2+  sparks. FPL induced pulmonary arterial contractions in all groups were sensitive to NIF. However, when compared with 125 mM K + , FPL contractions were greater in fetuses than in adults. FPL reduced Ca 2+  oscillations in myocytes of adult but not fetal arteries, independently of altitude. The FPL effects on Ca 2+  oscillations were reversed by NIF in myocytes of hypoxic but not normoxic adults. FPL failed to enhance Ca 2+  spark frequency and had little impact on spatiotemporal firing characteristics. These data suggest that Ca L -dependent contractions are largely uncoupled from intracellular Ca 2+  oscillations and the development of Ca 2+  sparks. This raises questions regarding the coupling of pulmonary arterial contractility to membrane depolarization, attendant Ca L  facilitation, and the related associations with the activation of Ca 2+  oscillations and Ca 2+  sparks.

american journal of physiology. regulatory, integrative and comparative physiology/american journal of physiology. regulatory, integrative, and comparative physiology

Long-term high-altitude hypoxia influences pulmonary arterial L-type calcium channel-mediated Ca<sup>2+</sup> signals and contraction in fetal and adult sheep

Long-term high-altitude hypoxia influences pulmonary arterial L-type calcium channel-mediated Ca2+ signals and contraction in fetal and adult sheep

Long-term high-altitude hypoxia influences pulmonary arterial L-type calcium channel-mediated Ca²⁺ signals and contraction in fetal and adult sheep