title: Expression of BK(Ca) channels in human pulmonary arteries: relationship with remodeling and hypoxic pulmonary vasoconstriction.
abstract: BACKGROUND
  Potassium channels are important in pulmonary circulation because they have been closely related to hypoxic pulmonary vasoconstriction (HPV). The objective of the study was to determine whether structural changes in pulmonary arteries (PA), such as those observed in patients with chronic obstructive pulmonary disease (COPD), might be associated with changes in the mRNA expression of both BK(Ca) and K(V) channels and their potential relationship with HPV.
  
  
  METHODS
  PA (about 1.5 mm in diameter) were obtained from 16 patients who underwent resective lung surgery. Intimal thickening was evaluated morphometrically. mRNA expression of BK(Ca), K(V)1.2, K(V)1.5, K(V)2.1 and K(V)3.1 was evaluated by RT-PCR in PA homogenates. Endothelial function and HPV were assessed in vitro in isolated PA using an organ bath.
  
  
  RESULTS
  Intimal enlargement was closely associated with an increase in the expression of BK(Ca) channel (r=0.57, p<0.05). Pulmonary arteries incubated with charybdotoxin, a BK(Ca) channel blocking agent, showed lower response to endothelium-dependent vasodilators indicating its contribution to reduce vascular tone. Pulmonary arteries with more pronounced responses to hypoxia were those with greater gene expression of BK(Ca) channels, suggesting a potential role in attenuating HPV (r=0.52, p<0.05). No changes in the expression of K(V) channels were found in remodeled arteries.
  
  
  CONCLUSIONS
  Structural changes of PA in COPD could alter the response to hypoxia due to changes in BK(Ca) potassium channel distribution. Since BK(Ca) channels contribute to diminish vascular tone, their increased expression in remodeled PA might play a role in attenuating HPV.
authors: Departments of Pulmonary Medicine and Pathology, Ciber de Enfermedades Respiratorias, Hospital Clínic, Institut d'Investigacions Biomèdiques Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain. vpeinado@clinic.ub.es
authors: Víctor I
authors: VI
authors: Peinado
authors: Raquel
authors: R
authors: París
authors: Josep
authors: J
authors: Ramírez
authors: Josep
authors: J
authors: Roca
authors: Robert
authors: R
authors: Rodriguez-Roisin
authors: Joan A
authors: JA
authors: Barberà
mesh_terms: D000368:Aged; D015153:Blotting, Western; D018999:Charybdotoxin / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology; D007120:Immunochemistry; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D009638:Norepinephrine / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011189:Potassium Chloride / Q000494:pharmacology; D011651:Pulmonary Artery / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
chemical_list: D024681:Potassium Channels, Calcium-Activated; D012333:RNA, Messenger; D018999:Charybdotoxin; D011189:Potassium Chloride; D006632:Histamine; D009638:Norepinephrine