title: P2Y₁ and P2Y₁₂ receptors in hypoxia- and adenosine diphosphate-induced pulmonary vasoconstriction in vivo in the pig.
abstract: OBJECTIVE
  To investigate the role of P2Y₁ and P2Y₁₂ receptors in hypoxia- and adenosine diphosphate (ADP)-induced pulmonary vasoconstriction.
  
  
  METHODS
  19 anaesthetized, mechanically ventilated pigs (31.3 ± 0.7 kg) were evaluated in normoxia and hypoxia, without (n = 6) or with P2Y₁ receptor antagonist MRS2500 (n = 7) or P2Y₁₂ receptor antagonist cangrelor (n = 6) treatment. 12 pigs (29.3 ± 0.4 kg) were evaluated before and during ADP infusion, without and with MRS2500 (n = 6) or cangrelor (n = 6) pre-treatment.
  
  
  RESULTS
  Hypoxia increased (p < 0.05) mean pulmonary artery pressure (MPAP) by 14.2 ± 1.1 mmHg and pulmonary vascular resistance (PVR) by 2.7 ± 0.4 WU. Without treatment MPAP and PVR remained unaltered (p = ns) for 90 min hypoxia. During hypoxia MRS2500 decreased (p < 0.013) MPAP by 4.3 ± 1.2 mmHg within 15 min. Cangrelor decreased (p < 0.036) MPAP to be 3.3 ± 0.4 and 3.6 ± 0.6 mmHg lower than hypoxia baseline after 10 and 30 min. PVR was, however, unaltered (p = ns) by MRS2500 or cangrelor during hypoxia. ADP increased (p < 0.001) MPAP and PVR to stabilize 11.1 ± 1.3 mmHg and 2.7 ± 0.3 WU higher than baseline. MRS2500 or cangrelor pre-treatment totally abolished the sustained MPAP- and PVR-increases to ADP.
  
  
  CONCLUSIONS
  ADP elicits pulmonary vasoconstriction through P2Y₁ and P2Y₁₂ receptor activation. ADP is not a mandatory modulator, but may still contribute to pulmonary vascular tone during acute hypoxia. Further investigations into the mechanisms behind ADP-induced pulmonary vasoconstriction and the role of ADP as a modulator of pulmonary vascular tone during hypoxia are warranted.
authors.affiliation: The Öresund Cardiovascular Research Collaboration, The Section for Heart Failure and Valvular Disease, The Clinic for Heart- and Lung Disease, Skåne University Hospital, 221 85, Lund, Sweden, david.kylhammar@med.lu.se.
authors.forename: David
authors.initials: D
authors.lastname: Kylhammar
authors.forename: Laurids T
authors.initials: LT
authors.lastname: Bune
authors.forename: Göran
authors.initials: G
authors.lastname: Rådegran
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D000249:Adenosine Monophosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure; D003838:Deoxyadenine Nucleotides / Q000494:pharmacology; D006976:Hypertension, Pulmonary / Q000378:metabolism / Q000503:physiopathology; D000860:Hypoxia / Q000378:metabolism* / Q000503:physiopathology; D011651:Pulmonary Artery / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D058921:Purinergic P2Y Receptor Antagonists / Q000494:pharmacology; D058472:Receptors, Purinergic P2Y1 / Q000378:metabolism*; D058925:Receptors, Purinergic P2Y12 / Q000378:metabolism*; D013552:Swine; D014661:Vasoconstriction
chemical_list: C495475:2-iodo-N(6)-methyl-(N)-methanocarba-2'-deoxyadenosine-3',5'-bisphosphate; D003838:Deoxyadenine Nucleotides; D058921:Purinergic P2Y Receptor Antagonists; D058472:Receptors, Purinergic P2Y1; D058925:Receptors, Purinergic P2Y12; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; C117446:cangrelor