title: Store-operated channels in the pulmonary circulation of high- and low-altitude neonatal lambs.
abstract: We determined whether store-operated channels (SOC) are involved in neonatal pulmonary artery function under conditions of acute and chronic hypoxia, using newborn sheep gestated and born either at high altitude (HA, 3,600 m) or low altitude (LA, 520 m). Cardiopulmonary variables were recorded in vivo, with and without SOC blockade by 2-aminoethyldiphenylborinate (2-APB), during basal or acute hypoxic conditions. 2-APB did not have effects on basal mean pulmonary arterial pressure (mPAP), cardiac output, systemic arterial blood pressure, or systemic vascular resistance in both groups of neonates. During acute hypoxia 2-APB reduced mPAP and pulmonary vascular resistance in LA and HA, but this reduction was greater in HA. In addition, isolated pulmonary arteries mounted in a wire myograph were assessed for vascular reactivity. HA arteries showed a greater relaxation and sensitivity to SOC blockers than LA arteries. The pulmonary expression of two SOC-forming subunits, TRPC4 and STIM1, was upregulated in HA. Taken together, our results show that SOC contribute to hypoxic pulmonary vasoconstriction in newborn sheep and that SOC are upregulated by chronic hypoxia. Therefore, SOC may contribute to the development of neonatal pulmonary hypertension. We propose SOC channels could be potential targets to treat neonatal pulmonary hypertension.
authors: Laboratorios de Fisiología y Fisiopatología del Desarrollo, y de Bioquímica y Biología Molecular de la Hipoxia, Programa de Fisiopatología, Instituto de Ciencias Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago, Chile.
authors: Daniela
authors: D
authors: Parrau
authors: Germán
authors: G
authors: Ebensperger
authors: Emilio A
authors: EA
authors: Herrera
authors: Fernando
authors: F
authors: Moraga
authors: Raquel A
authors: RA
authors: Riquelme
authors: César E
authors: CE
authors: Ulloa
authors: Rodrigo T
authors: RT
authors: Rojas
authors: Pablo
authors: P
authors: Silva
authors: Ismael
authors: I
authors: Hernandez
authors: Javiera
authors: J
authors: Ferrada
authors: Marcela
authors: M
authors: Diaz
authors: Julian T
authors: JT
authors: Parer
authors: Gertrudis
authors: G
authors: Cabello
authors: Aníbal J
authors: AJ
authors: Llanos
authors: Roberto V
authors: RV
authors: Reyes
mesh_terms: D000531:Altitude; D000532:Altitude Sickness / Q000097:blood / Q000150:complications / Q000235:genetics / Q000503:physiopathology; D000818:Animals; D000831:Animals, Newborn; D001896:Boron Compounds / Q000494:pharmacology; D004195:Disease Models, Animal; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006801:Humans; D000860:Hypoxia / Q000097:blood / Q000150:complications / Q000235:genetics / Q000503:physiopathology; D007231:Infant, Newborn; D007473:Ion Channels / Q000097:blood / Q000235:genetics / Q000502:physiology*; D010547:Persistent Fetal Circulation Syndrome / Q000097:blood / Q000209:etiology / Q000503:physiopathology; D011651:Pulmonary Artery / Q000503:physiopathology; D011652:Pulmonary Circulation / Q000187:drug effects / Q000502:physiology*; D034561:Sheep, Domestic / Q000097:blood / Q000235:genetics / Q000502:physiology*; D050052:TRPC Cation Channels / Q000097:blood / Q000502:physiology; D014661:Vasoconstriction / Q000502:physiology
chemical_list: C538758:2-aminoethyl diphenylborinate; D001896:Boron Compounds; D007473:Ion Channels; D050052:TRPC Cation Channels; C489571:TRPC4 ion channel