title: Role of the gap junctions in the contractile response to agonists in pulmonary artery from two rat models of pulmonary hypertension.
abstract: BACKGROUND
  Pulmonary hypertension (PH) is characterized by arterial vascular remodelling and alteration in vascular reactivity. Since gap junctions are formed with proteins named connexins (Cx) and contribute to vasoreactivity, we investigated both expression and role of Cx in the pulmonary arterial vasoreactivity in two rat models of PH.
  
  
  METHODS
  Intrapulmonary arteries (IPA) were isolated from normoxic rats (N), rats exposed to chronic hypoxia (CH) or treated with monocrotaline (MCT). RT-PCR, Western Blot and immunofluorescent labelling were used to study the Cx expression. The role of Cx in arterial reactivity was assessed by using isometric contraction and specific gap junction blockers. Contractile responses were induced by agonists already known to be involved in PH, namely serotonin, endothelin-1 and phenylephrine.
  
  
  RESULTS
  Cx 37, 40 and 43 were expressed in all rat models and Cx43 was increased in CH rats. In IPA from N rats only, the contraction to serotonin was decreased after treatment with 37-43Gap27, a specific Cx-mimetic peptide blocker of Cx 37 and 43. The contraction to endothelin-1 was unchanged after incubation with 40Gap27 (a specific blocker of Cx 40) or 37-43Gap27 in N, CH and MCT rats. In contrast, the contraction to phenylephrine was decreased by 40Gap27 or 37-43Gap27 in CH and MCT rats. Moreover, the contractile sensitivity to high potassium solutions was increased in CH rats and this hypersensitivity was reversed following 37-43Gap27 incubation.
  
  
  CONCLUSIONS
  Altogether, Cx 37, 40 and 43 are differently expressed and involved in the vasoreactivity to various stimuli in IPA from different rat models. These data may help to understand alterations of pulmonary arterial reactivity observed in PH and to improve the development of innovative therapies according to PH aetiology.
authors.affiliation: INSERM, U1045, F-33076 Bordeaux, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Billaud
authors.forename: Diana
authors.initials: D
authors.lastname: Dahan
authors.forename: Roger
authors.initials: R
authors.lastname: Marthan
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Savineau
authors.forename: Christelle
authors.initials: C
authors.lastname: Guibert
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015153:Blotting, Western; D018031:Connexin 43 / Q000378:metabolism; D017630:Connexins / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000494:pharmacology*; D005455:Fluorescent Antibody Technique; D017629:Gap Junctions / Q000187:drug effects* / Q000378:metabolism; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D000860:Hypoxia / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D016686:Monocrotaline; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D010656:Phenylephrine / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012701:Serotonin / Q000378:metabolism / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D000097003:Gap Junction alpha-5 Protein; D000097006:Gap Junction alpha-4 Protein
chemical_list: D018031:Connexin 43; D017630:Connexins; D019332:Endothelin-1; D016686:Monocrotaline; D010656:Phenylephrine; D012701:Serotonin; D014662:Vasoconstrictor Agents; D000097003:Gap Junction alpha-5 Protein; D000097006:Gap Junction alpha-4 Protein