title: T-type calcium channels are involved in hypoxic pulmonary hypertension.
abstract: OBJECTIVE
  Pulmonary hypertension (PH) is the main disease of pulmonary circulation. Alteration in calcium homeostasis in pulmonary artery smooth muscle cells (PASMCs) is recognized as a key feature in PH. The present study was undertaken to investigate the involvement of T-type voltage-gated calcium channels (T-VGCCs) in the control of the pulmonary vascular tone and thereby in the development of PH.
  
  
  RESULTS
  Experiments were conducted in animals (rats and mice) kept 3-4 weeks in either normal (normoxic) or hypoxic environment (hypobaric chamber) to induce chronic hypoxia (CH) PH. In vivo, chronic treatment of CH rats with the T-VGCC blocker, TTA-A2, prevented PH and the associated vascular hyperreactivity, pulmonary arterial remodelling, and right cardiac hypertrophy. Deletion of the Cav3.1 gene (a T-VGCC isoform) protected mice from CH-PH. In vitro, patch-clamp and PCR experiments revealed the presence of T-VGCCs (mainly Cav3.1 and Cav3.2) in PASMCs. Mibefradil, NNC550396, and TTA-A2 inhibited, in a concentration-dependent manner, T-VGCC current, KCl-induced contraction, and PASMC proliferation.
  
  
  CONCLUSIONS
  The present study demonstrates that T-VGCCs contribute to intrapulmonary vascular reactivity and is implicated in the development of hypoxic PH. Specific blockers of T-VGCCs may thus prove useful for the therapeutic management of PH.
authors.affiliation: Université de Bordeaux, Centre de Recherche Cardio-Thoracique de Bordeaux, U 1045, Bordeaux F-33000, France INSERM, Centre de Recherche Cardio-Thoracique de Bordeaux, 1045, Bordeaux, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Chevalier
authors.affiliation: Université de Bordeaux, Centre de Recherche Cardio-Thoracique de Bordeaux, U 1045, Bordeaux F-33000, France INSERM, Centre de Recherche Cardio-Thoracique de Bordeaux, 1045, Bordeaux, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Gilbert
authors.affiliation: Université de Bordeaux, Centre de Recherche Cardio-Thoracique de Bordeaux, U 1045, Bordeaux F-33000, France INSERM, Centre de Recherche Cardio-Thoracique de Bordeaux, 1045, Bordeaux, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Roux
authors.affiliation: CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier, France.
authors.forename: Philipe
authors.initials: P
authors.lastname: Lory
authors.affiliation: Université de Bordeaux, Centre de Recherche Cardio-Thoracique de Bordeaux, U 1045, Bordeaux F-33000, France INSERM, Centre de Recherche Cardio-Thoracique de Bordeaux, 1045, Bordeaux, France CHU Bordeaux, Exploration Fonctionnelle Respiratoire, Bordeaux, France.
authors.forename: Roger
authors.initials: R
authors.lastname: Marthan
authors.affiliation: Université de Bordeaux, Centre de Recherche Cardio-Thoracique de Bordeaux, U 1045, Bordeaux F-33000, France INSERM, Centre de Recherche Cardio-Thoracique de Bordeaux, 1045, Bordeaux, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Savineau
authors.affiliation: Université de Bordeaux, Centre de Recherche Cardio-Thoracique de Bordeaux, U 1045, Bordeaux F-33000, France INSERM, Centre de Recherche Cardio-Thoracique de Bordeaux, 1045, Bordeaux, France jean-francois.quignard@u-bordeaux2.fr.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Quignard
mesh_terms: D000818:Animals; D044482:Benzeneacetamides / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D020747:Calcium Channels, T-Type / Q000378:metabolism*; D004195:Disease Models, Animal; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology*; D000860:Hypoxia / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D011651:Pulmonary Artery / Q000187:drug effects* / Q000503:physiopathology; D011725:Pyridines / Q000494:pharmacology; D017208:Rats, Wistar
chemical_list: C553486:2-(4-cyclopropylphenyl)-N-(1-(5-((2,2,2-trifluoroethyl)oxo)pyridin-2-yl)ethyl)acetamide; D044482:Benzeneacetamides; D020747:Calcium Channels, T-Type; D011725:Pyridines; D002118:Calcium
keywords: Arterial reactivity; Calcium channel blockers; Patch-clamp; Pulmonary circulation; T-type calcium currents