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European Journal of Applied Physiology

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01-09-2014 | Original Article

P2Y₁ and P2Y₁₂ receptors in hypoxia- and adenosine diphosphate-induced pulmonary vasoconstriction in vivo in the pig

Authors: David Kylhammar, Laurids T. Bune, Göran Rådegran

Published in: European Journal of Applied Physiology | Issue 9/2014

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.

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Title: P2Y1 and P2Y12 receptors in hypoxia- and adenosine diphosphate-induced pulmonary vasoconstriction in vivo in the pig
Authors: David Kylhammar
Laurids T. Bune
Göran Rådegran
Publication date: 01-09-2014
Publisher: Springer Berlin Heidelberg
Published in: European Journal of Applied Physiology / Issue 9/2014
Print ISSN: 1439-6319
Electronic ISSN: 1439-6327
DOI: https://doi.org/10.1007/s00421-014-2921-y

At a glance: The STEP trials

Springer Medicine

P2Y₁ and P2Y₁₂ receptors in hypoxia- and adenosine diphosphate-induced pulmonary vasoconstriction in vivo in the pig

Abstract

Purpose

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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