David Kylhammar1, Laurids T Bune, Göran Rådegran. 1. 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.
Abstract
PURPOSE: 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.
PURPOSE: 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.
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